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Genetic Factors (genetic + factor)
Kinds of Genetic Factors Selected AbstractsSTUDY OF THE RELATIONSHIP BETWEEN THE KAZAKH'S LIFESTYLE AND GENETIC FACTORS, AND HYPERTENSION, IN THE NORTH-WEST OF CHINACLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007NF Li SUMMARY 1We investigated the relationship between genetic and environmental factors in hypertensive people living in the Xinjiang Uygur Autonomous Region of China. 2Body mass index, alcohol intake, serum total cholesterol, low-density lipoprotein-cholesterol and triglyceride level in the hypertensive group were significantly higher than corresponding values in the normal group. 3Angiotensinogen gene polymorphisms and related haplotype H6 and H9 were strongly associated with essential hypertension. The b2 -adrenergic receptor gene was associated with lipid disorders in Kazakhs in Xinjiang. 4The results suggest that both genetic and environmental factors play an important role in the development of hypertension in Kazakhs in Xinjiang. [source] Do Genetic Factors Influence Religious Life?JOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION, Issue 4 2008Findings from a Behavior Genetic Analysis of Twin Siblings Social scientific research assumes that religious involvement is primarily, if not exclusively, the product of social-environmental influences There is growing evidence, however, that genetic or other biological factors also play a role Analyzing twin sibling data from the National Survey of Midlife Development in the United States (MIDUS), this study addresses this issue by showing that individual-level variation on four different aspects of religious life,organizational involvement, personal religiosity and spirituality, conservative ideologies, and transformations and commitments,is indeed the product of both genetic and environmental influences Specifically, genetic factors explain 19,65 percent of the variation, while environmental influences account for the remaining 35,81 percent depending upon the aspect of religion under investigation Research of this type enhances contemporary social science by providing a new perspective that nicely supplements existing ones, but it also highlights potential implications, including explanatory power deficiencies and potentially bias [source] Treatment of Idiopathic Cutaneous Hyperchromia of the Orbital Region (ICHOR) with Intense Pulsed LightDERMATOLOGIC SURGERY, Issue 6 2006NATALIA CYMROT CYMBALISTA MD BACKGROUND Idiopathic cutaneous hyperchromia of the orbital region (ICHOR) does not have a clear etiopathogenesis. Genetic factors, increased melanin, prominent vasculature, and eyelid skin slackness seem to be involved. OBJECTIVE To evaluate individuals with ICHOR clinically and histologically, before and after treatment with high-energy pulsed light (HEPL), considering epidermal and dermal melanin, in order to evaluate HEPL efficacy in clearing away ICHOR, and 1 month and 1 year later to check whether improvement was maintained. METHODS Twelve individuals with ICHOR underwent clinical and histological evaluation before and after HEPL application, with photographic comparison. They underwent one to four HEPL sessions on the lower eyelid at approximately 30-day intervals. Melanin quantification by area, before and after treatment was performed by digital image morphometry. RESULTS Eyelid skin was significantly lightened (p=.24), and was maintained 1 year later with no ICHOR reincidence. All individuals (100%) showed postinflammatory hyperchromia (average 6-month duration), while 58.33% presented hypochromia (7-month duration). There was significantly decreased epidermal and dermal melanin after treatment. CONCLUSION HEPL was shown to be useful in clearing up ICHOR. This was maintained after 1 year. Epidermal and dermal histopathology showed decreased melanin following treatment. Longer follow-up is needed to evaluate possible later recurrence of ICHOR. [source] A new look at viruses in type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2003Hee-Sook Jun Abstract Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of T1D, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of T1D. To date, 14 different viruses have been reported to be associated with the development of T1D in humans and animal models. Viruses may be involved in the pathogenesis of T1D in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, [e.g. Kilham rat virus (KRV)] and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, KRV, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus (EBV) are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] ACE and angiotensinogen gene genotypes and left ventricular mass in athletesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2001F. Diet Background Genetic factors may be important in modifying heart size due to long-term athletic training. The significance of polymorphisms of genes of the renin,angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known. Methods The angiotensin I-converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass. Results No association with left ventricular mass was found for the polymorphisms of angiotensin I-converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I-converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m,2) (P = 0·023). Athletes with the angiotensin I-converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179·8 ± 26·1 g m,2 vs. 145·2 ± 27·3 g m,2, P = 0·003). Conclusions These results suggest an association of combined angiotensin I-converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long-term athletic training. A synergistic effect of angiotensin I-converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur. [source] Genetic variants in the IMPA2 gene do not confer increased risk of febrile seizures in Caucasian patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007M. A. Blair Pathogenesis of febrile seizures (FS), causing the most common of types of seizures in children, remains unknown. Genetic factors appear to play a pivotal role and FS can be inherited as a monogenic or genetically complex disorder. Several risks factors have been proposed but many of the previously reported genetic associations were not replicated. Non-coding polymorphisms in the myo-inositol monophosphatase 2 gene (IMPA2) have been suggested as a susceptibility factor for FS in Japanese patients. It is unknown whether genetic variants in the same gene constitute a risk factor for FS in other ethnic groups because the frequency of FS is significantly higher in Japanese children than in Caucasian patients. We investigated the role of the IMPA2 gene in a cohort of 96 unrelated Caucasian subjects with a history of FS. We did not identify any significant differences in genotypes of cases and matched controls; no mutations or non-synonymous polymorphisms were detected in these individuals. Our data suggest that the genetic variants in the IMPA2 gene are not associated with a risk of FS in Caucasian patients and patients from various genetic groups are likely to have different genetic causes of FS. [source] Pharmacogenomics in dermatology: from susceptibility genes to personalized therapyEXPERIMENTAL DERMATOLOGY, Issue 4 2009Carlo Pincelli Abstract:, A significant proportion of patients with skin disease do not respond to treatment and adverse drug reactions are a common problem. Genetic factors are important determinants for both drug efficacy and toxicity. The fields of pharmacogenetics and pharmacogenomics examine inter-individual variations in the DNA sequence that are related to drug efficacy and toxicity. Here, we present pharmacogenomic data relevant to dermatology and explore the role of dermatologists in identifying patients who may respond to treatment or experience adverse drug reactions. [source] Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitisHEPATOLOGY, Issue 1 2002Arndt Vogel Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune-mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25-Dihydroxyvitamin D3 has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. In this study VDR polymorphisms were analyzed in 123 patients with AIH, 74 patients with PBC, and 214 controls. VDR polymorphisms were assessed by BsmI, TaqI, ApaI, and Fok endonuclease digestion after specific polymerase chain reaction (PCR) amplification. We found a significant association between the BsmI polymorphisms in PBC patients in comparison with controls (,2 = 9.49, P = .009). Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls (,2 = 9.71, P = .008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases. [source] Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of pubertyINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010A. Mouritsen Summary A recent decline in onset of puberty , especially among girls , has been observed, first in the US in the mid-1990s and now also in Europe. The development of breast tissue in girls occurs at a much younger age and the incidence of precocious puberty (PP) is increasing. Genetic factors and increasing prevalence of adiposity may contribute, but environmental factors are also likely to be involved. In particular, the widespread presence of endocrine-disrupting chemicals (EDCs) is suspected to contribute to the trend of earlier pubertal onset. The factors regulating the physiological onset of normal puberty are poorly understood. This hampers investigation of the possible role of environmental influences. There are many types of EDCs. One chemical may have more than one mode of action and the effects may depend on dose and duration of the exposure, as well as the developmental stage of the exposed individual. There may also be a wide range of genetic susceptibility to EDCs. Human exposure scenarios are complex and our knowledge about effects of mixtures of EDCs is limited. Importantly, the consequences of an exposure may not be apparent at the actual time of exposure, but may manifest later in life. Most known EDCs have oestrogenic and/or anti-androgenic actions and only few have androgenic or anti-oestrogenic effects. Thus, it appears plausible that they interfere with normal onset of puberty. The age at menarche has only declined by a few months whereas the age at breast development has declined by 1 year; thus, the time span from initiation of breast development to menarche has increased. This may indicate an oestrogen-like effect without concomitant central activation of the hypothalamic,pituitary axis. The effects may differ between boys and girls, as there are sex differences in age at onset of puberty, hormonal profiles and prevalence of precocius puberty. [source] Variation in the TNF Gene Promoter and Risk of Osteolysis After Total Hip ArthroplastyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2003FRCS, J Mark Wilkinson PhD Abstract Genetic factors may influence implant failure caused by osteolysis after THA. In an association study of 481 subjects after THA, we found that carriage of the TNF - 238A allele was associated with an increased incidence of osteolysis versus noncarriage (odds ratio, 1.7) and was independent of other risk factors. Genetic and environmental factors influence implant survival after THA. Introduction: Tumor necrosis factor (TNF) is thought to play a role in osteolysis, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at ,238 and ,308 in the TNF gene promoter are associated with differences in susceptibility to several TNF-mediated diseases. We tested whether these polymorphisms are associated with osteolysis after THA. Materials and Methods: A total of 481 whites (214 with failed versus 267 with intact implants) were recruited 11.7 ± 4 years after cemented THA. Genomic DNA was extracted from peripheral blood and genotyped for the ,238 and ,308 polymorphisms using the Taqman 5, nuclease method. Healthy controls (n = 500) from the background population were also genotyped to establish the local prevalence of these alleles. Results: The carriage of ,238A was 8.8% in the background population and 10.9% in the THA controls (p > 0.05). Carriage of ,238A in the osteolysis group was 17.3% (odds ratio, 1.7; 95% CI, 1.0,2.9). Carriage was highest (20.5%) in patients with more widespread osteolysis (OR, 2.1; 1.2,3.8). The association of ,238A with osteolysis was independent of other risk factors for osteolysis (logistic regression analysis: OR, 1.8; 1.0,3.2). Carriage of ,308A was not associated with osteolysis. Conclusion: Genetic, as well as environmental factors, influence implant failure after THA. Whether the TNF - 238 polymorphism causes a biological change that predisposes to loosening or is in linkage disequilibrium with such a locus is not yet known. [source] Perspective: Reconsidering the Effects of Antiresorptive Therapies in Reducing Osteoporotic FractureJOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2001C. H. Chesnut III Abstract Concepts of what constitutes osteoporosis have evolved from the single criterion of low bone mass to a more inclusive consideration of bone strength, based on both quantity and quality. The evidence driving this shift is drawn from many sources. For example, recent studies of bone geometry have shown what engineers have always known: material properties and structural strength are inseparable. Genetic factors also argue against a one-dimensional (1D) view of osteoporosis. Large-scale family studies present a strong case for genetic influences on bone mass and predisposition to fracture. The contribution of aging to fracture risk has long been known, but we are only now beginning to understand what happens to bone remodeling and microstructure in an aging skeleton. The recognition that osteoporosis is far more complex than previously thought suggests that factors in addition to bone mineral density (BMD) may be useful for evaluating bone fragility and therapeutic effectiveness. Although assessment of BMD is noninvasive and widely available, the degree of increase in BMD alone fails to account for the broader effectiveness of antiresorptive agents in reducing the risk of fractures related to osteoporosis. Indeed, the very multiplicity of factors that determine fracture risk implies that response to therapy may be equally complex. Studies of response to antiresorptive agents and the cellular processes they induce are at best preliminary at this time. Although new technologies have been applied to studying bone microarchitecture, their invasive nature limits wide use. New methods are needed to provide insight into the causes and effects of bone fragility. The definition of osteoporosis, meanwhile, must still be considered a work in progress. [source] Sister chromatid exchange and micronucleus studies in patients with Behçet's diseaseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2009Ali Karaman Background:, Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The aim of this study was to determine, by counting sister chromatid exchange (SCE) and micronucleus (MN) frequencies, whether DNA damage have an effect on the pathogenesis of BD. Furthermore, our aim was to show if there is an association between oxidative stress and chromosome instability in BD. Methods:, We analyzed lymphocytes from patients with BD (16 in active and 14 in inactive periods) and 20 healthy controls for SCE and MN frequencies. In addition, malondialdehyde (MDA) level, superoxide dismutase (SOD) level, glutathione peroxidase (GSH-Px) activity, erythrocyte sedimentation rate (ESR) and polymorphonuclear leukocyte (PMNL) count were determined in the all subjects. Results:, The SCE and MN frequencies were significantly higher in both the active and inactive period patients than in the controls (p < 0.00001, p < 0.0001, p < 0.01 and p < 0.05, respectively), and the MDA level was significantly higher in both the active and inactive period patients than in the controls (p < 0.01 and p < 0.05, respectively). In contrast, the SOD and GSH-Px levels were significantly lower in both the active and inactive period patients than in the controls (p < 0.01, p < 0.05, p < 0.01 and p < 0.05, respectively). Conclusions:, Our results suggest that increased plasma MDA level and decreased plasma GSH-Px and SOD levels reflect the increased levels of oxidative stress in BD patients, and this situation may impair genetic stability in BD patients. [source] Conservation goals and fisheries management units for Atlantic salmon in the Baltic Sea areaJOURNAL OF FISH BIOLOGY, Issue 2001M-L. Koljonen The effective application of genetic information in fisheries management strategies implies political goal setting taking both conservation and fisheries management into account. The concept of sustainable use as set out by the Convention on Biological Diversity offers a valuable starting point in this respect, since the criterion for it is defined as the maintenance of genetic diversity within each species. However, strategic decisions are also needed on the practical level, where the actual genetic information can be taken into account. Genetic factors, such as glacial differentiation, the postglacial genetic structure of populations, gene flow levels and the probability of the existence of adaptive differences, have an effect on the formation of conservation and management units and on the long-term strategy for the sustainable use of aspecies. The Atlantic salmon (Salmo salar) in the Baltic Sea area is treated here as an example of a complicated management problem with a highly hierarchical genetic structure associated with marked loss of naturally reproductive stocks, extensive hatchery production and an effective international offshore fishery. The implications of genetic factors for the conservation and management strategy of the Baltic salmon is discussed in the light of the goals set by the Convention on Biological Diversity, the Straddling Fish Stocks and Highly Migratory Fish Stocks Agreement, the Habitats Directive of the European Union and the International Baltic Sea Fishery Commission. [source] A common haplotype of the C-C chemokine receptor 2 gene and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndromeJOURNAL OF INTERNAL MEDICINE, Issue 5 2008P. Spagnolo Abstract. Aim., Sarcoidosis is a heterogeneous disorder with a strong genetic influence. Genetic factors are also thought to influence disease severity and outcome. We sought to determine whether polymorphisms within CCR2 gene predispose to Löfgren's syndrome , a clinically and genetically distinct sarcoidosis phenotype , and, importantly, whether this association is independent of the known association with the HLA-DRB1*0301 allele. Methods., We investigated 5 CCR2 variants and HLA-DRB1*0301 by sequence-specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 Löfgren's syndrome, 100 controls) and 387 Swedish subjects (126 Löfgren's syndrome, 77 non-Löfgren sarcoidosis, 184 controls). Results., One of the deduced haplotypes (CCR2 haplotype 2) was associated with Löfgren's syndrome in both Spanish (OR: 2.03, uncorrected P = 0.02; permuted P = 0.041 vs. controls) and Swedish patients (OR: 3.02, uncorrected P = 0.0007; permuted P = 0.0027 vs. non-Löfgren sarcoidosis; OR: 2.46, uncorrected P = 0.0005; permuted P = 0.0031 vs. controls). HLA-DRB1*0301 allele frequency was also increased in Spanish (OR: 3.52, P = 0.0004 vs. controls) and Swedish patients with Löfgren's syndrome (OR: 10.98, P < 0.0001 vs. non-Löfgren sarcoidosis, OR: 7.71, P < 0.0001 vs. controls). Finally, multivariate analysis revealed that the CCR2 association was independent of HLA-DRB1*0301 in both Spanish (P = 0.02 vs. controls) and Swedish cohorts (P = 0.002 vs. non-Löfgren sarcoidosis, P = 0.001 vs. controls). Conclusions., This study confirms that CCR2 haplotype 2 and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndrome. [source] Febrile seizures are associated with mutation of seizure-related (SEZ) 6, a brain-specific geneJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2007Zhi-liang Yu Abstract Genetic factors contribute significantly to the etiology of febrile seizures (FS), the most common type of seizures in childhood. However, in most patients with FS, the causative gene is unknown. The purpose of this study was to explore the relationship between human brain-specific gene SEZ-6 and FS. Through amplification of genomic DNA by PCR and sequencing of the resulting products, we screened 75 subjects for mutations in the coding region (17 exons) of the SEZ-6 gene. Fifteen subjects were healthy individuals and 60 subjects had FS. Patients with FS could be divided into sub-groups based on seizure type (42 simple and 18 complex) and family history (41 had a positive family history). All patients have been followed to date to evaluate seizure recurrence and the development of epilepsy. No mutations were found in healthy controls, but 21 of the patients with FS had mutations in SEZ-6, and the most common type of mutation was a heterozygous, cytosine insertion (frame shift mutation) at position 1435 of the cDNA. The mutation incidence was significantly higher in patients with complex FS (vs. simple FS) and in patients with a positive family history. Sixteen of 42 patients with simple FS experienced seizure recurrence during the 1,5-year follow-up period. Fifteen of 18 patients with complex FS also experienced a recurrence during this period. Among these patients with recurrences, five patients with simple FS and six patients with complex FS have developed epilepsy. The mutation incidence among these epileptic patients is 72.7%. The human SEZ-6 gene is related to the occurrence and development of FS and may be a novel candidate gene for epilepsy. Screening for mutations in SEZ-6 may be valuable in predicting FS recurrence or the development of epilepsy. © 2006 Wiley-Liss, Inc. [source] The Relationship Between Genetic Influences on Alcohol Dependence and on Patterns of Alcohol ConsumptionALCOHOLISM, Issue 6 2010Kenneth S. Kendler Background:, Genetic factors impact substantially both on alcohol consumption (AC) and on the risk for alcohol dependence (AD). However, we know little about the degree to which measures of AC index the genetic risk for AD. Methods:, We assessed a lifetime history of AD by DSM-IV criteria and four measures of AC at the time of heaviest drinking (drink frequency, regular quantity, maximum quantity, and drunk frequency) in 5,073 adult twins from same-sex pairs from the Virginia Twin Registry. Structural models were fitted using Mx. Results:, We found evidence for different genetic structure in the sexes. In women, genetic risk for AD and for the four measures of AC was entirely shared. In men, the AC measures captured 85% of the genetic risk for AD. In women, the genetic relationship with AD was strongest for drunk frequency and in men for both drunk frequency and regular quantity. Conclusions:, In a population-based sample of twins, four relatively simple measures of AC obtained for the time of lifetime heaviest drinking were able to capture all (in women) or a very large proportion (in men) of the genetic risk for the complex multi-dimensional construct of AD. If replicated, these results have practical implications for studies aiming to assess genetic risk for AD. [source] Intellectual Disability in the Context of a South African PopulationJOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES, Issue 2 2008Jennifer Kromberg Abstract, Childhood disabilities, including intellectual disabilities (ID), are thought to occur in 5,17% of children in developing countries around the world. In order to identify and describe the childhood disabilities occurring in a rural South African population, as well as the context in which they occur, a study was carried out in the Bushbuckridge district in the poor northeast part of the country. Altogether, 6,692 children were screened in their homes in eight villages using the Ten Questions questionnaire. This questionnaire was used by local-trained field-workers in interviews with mothers and other carers, to screen children for five disorders (viz., intellectual, hearing, visual and movement disorders, and epilepsy). Altogether, 722 (10.8% of the total sample) children, who screened positive, were examined at clinics in their villages by a pediatrician for diagnostic, treatment, and referral purposes. In addition, 100 traditional healers in the district were interviewed with a specially designed schedule of questions to assess their attitudes toward disabilities and their management of affected children. The results showed that 291 (4.3%) children had at least one of the five disabilities. ID occurred in 3.6%, epilepsy in 0.7%, visual disorders in 0.5%, movement disorders in 0.5%, and hearing disorders in 0.3%. More boys than girls with hearing disorders were receiving special education. Many of the affected children were not receiving treatment or education, resulting in a reduction in their quality of life. Traditional healers were attempting to treat epilepsy and seldom referred affected children to hospital, although effective treatment was available there. Genetic factors were involved in about half the conditions, but genetic services were negligible. Appropriate health, diagnostic, treatment, educational, and supportive services are required for children with disabilities, and awareness of their needs and the resources to meet them should be increased in this community. [source] Spousal Concordance for Alcohol Dependence: Evidence for Assortative Mating or Spousal Interaction Effects?ALCOHOLISM, Issue 5 2007Julia D. Grant Background: Alcohol dependence (AD) is among the most common psychiatric disorders, and impacts the health and well-being of problem drinkers, their family members, and society as a whole. Although previous research has consistently indicated that genetic factors contribute to variance in risk for AD, little attention has been paid to nonrandom mating for AD. When assortative mating occurs for a heritable trait, spouses are genetically correlated and offspring are at increased risk of receiving high-risk genes from both parents. The primary goal of the present analyses is to test hypotheses about the source(s) and magnitude of spousal associations for AD using a twin-spouse design. Methods: DSM-IV AD (without the clustering criterion) was assessed via telephone interview for 5,974 twin members of an older cohort of the Australian Twin Register (born 1902,1964) and 3,814 spouses of the twins. Quantitative genetic modeling was used to determine the extent to which variability in risk for AD was influenced by genetic factors, the extent of spousal association for AD, and whether the association was attributable to assortative mating, reciprocal spousal interaction, or both processes. Results: Genetic factors explained 49% of the variance in risk for AD. There was no evidence of gender differences in the spousal interaction effect, the degree of rater bias, or the association between the twin's report of spouse AD and the spouse's AD phenotype. Either the assortative mating parameter or the spousal interaction parameter could be removed from the model without a significant decrement in fit, but both could not be dropped simultaneously, suggesting a lack of power to differentiate between these 2 causes of spousal correlation. When both effects were included in the model, the spousal correlation was 0.29, the assortative mating coefficient was 0.45 (i.e., "like marries like"), and the reciprocal spousal interaction coefficient was ,0.10 (i.e., after controlling for assortative mating, the additional impact of spousal interactions is slightly protective). Conclusions: These analyses provide evidence of significant spousal associations for AD, with assortative mating increasing spouse similarity and spousal interaction effects decreasing it after controlling for assortative mating. Although the genetic impact is modest, assortative mating results in an increased proportion of offspring exposed to 2 alcoholic parents and the associated detrimental environmental sequelae, and increases the likelihood of offspring inheriting high-risk genes from both parents. [source] Gene-Environment Interaction in Patterns of Adolescent Drinking: Regional Residency Moderates Longitudinal Influences on Alcohol UseALCOHOLISM, Issue 5 2001Richard J. Rose Background: Drinking frequency escalates rapidly during adolescence. Abstinence declines markedly, and drinking monthly or more often becomes normative. Individual differences in adolescent drinking patterns are large, and some patterns are predictive of subsequent drinking problems; little, however, is known of the gene,environment interactions that create them. Methods: Five consecutive and complete birth cohorts of Finnish twins, born 1975,1979, were enrolled sequentially into a longitudinal study and assessed, with postal questionnaires, at ages 16, 17, and 18.5 years. The sample included 1786 same-sex twin pairs, of whom 1240 pairs were concordantly drinking at age 16. Maximum likelihood models were fit in longitudinal analyses of the three waves of drinking data to assess changes in genetic and environmental influences on alcohol use across adolescence. Secondary analyses contrasted twin pairs residing in rural versus those in urban environments to investigate gene,environment interactions. Results: Longitudinal analyses revealed that genetic factors influencing drinking patterns increased in importance across the 30-month period, and effects arising from common environmental influences declined. Distributions of drinking frequencies in twins residing in urban and rural environments were highly similar, but influences on drinking varied between the two environments. Genetic factors assumed a larger role among adolescents residing in urban areas, while common environmental influences were more important in rural settings. Formal modeling of the data established a significant gene,environment interaction. Conclusions: The results document the changing impact of genetic and environmental influences on alcohol use across adolescence. Importantly, the results also reveal a significant gene,environment interaction in patterns of adolescent drinking and invite more detailed analyses of the pathways and mechanisms by which environments modulate genetic effects. [source] Genetic factors in human obesityOBESITY REVIEWS, Issue 2007I. S. Farooqi [source] Genetic factors associated with skin cancer in renal transplant patientsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2-3 2007Mary Elizabeth Laing Background: Non-melanoma skin cancer represents a significant cause of morbidity and mortality among renal transplant recipients. Established risk factors that increase susceptibility to skin cancer after transplantation include skin type, sun exposure and level of immunosuppression. Methods: A comprehensive literature review was carried out to discuss relevant genetic polymorphism for the development of skin cancer in organ transplant recipients. These include genetic polymorphisms in glutathione S -transferase, interleukin-10, retinoblastoma and p53 genes. We also discuss genetic polymorphisms in the folate pathway, melanocortin 1 receptor and vitamin D receptor recently discovered in our group. Results: No single factor is causative in cutaneous carcinogenesis in transplant recipients. Interactions of some of the above mechanisms with known environmental factors lead to increased risk. Conclusion: Polymorphisms in methylenetetrahydrofolate reductase are potentially correctable with folic acid supplementation; however, further evaluation is required in adequately powered prospective clinical trials. Avoidance of known oncogenic environmental factors and genetic risk evaluation may improve outcomes in transplant patients. [source] Familial aggregation of olfactory impairment and odor identification in older adults,THE LARYNGOSCOPE, Issue 8 2010Laura A. Raynor MS Abstract Objectives/Hypothesis: The objective of this analysis was to estimate the genetic contributions to olfactory impairment. Study Design: Population based. Methods: Olfactory impairment was measured using the San Diego Odor Identification Test at the 5-year follow-up examination for the population-based Epidemiology of Hearing Loss study. Subjects were classified as impaired if they correctly identified fewer than six out of eight odorants. To reduce confounding by age, analysis was restricted to subjects who were 60 to 79 years of age. Familial aggregation was evaluated by heritability estimates, tetrachoric correlations, and odds ratios in 207 sibling pairs from 135 sibships. Results: The prevalence of olfactory impairment was 20.2% overall and was higher in men. After adjustment for sex, age, and smoking, heritability of olfactory impairment was moderate (h2 = 0.55), although not statistically significantly different from 0 (P = .09). By contrast, the adjusted heritability estimate for bubble gum, one of the individual odorants, was significant (h2 = 0.51; P = .01). Conclusions: Genetic factors might contribute to general olfactory impairment in older adults, but the strength of familial aggregation differs for individual odorants, a finding consistent with prior research. Laryngoscope, 2010 [source] Albatrosses, eagles and newts, Oh My!: exceptions to the prevailing paradigm concerning genetic diversity and population viability?ANIMAL CONSERVATION, Issue 5 2010D. H. Reed Abstract Numerous recent papers have demonstrated a central role for genetic factors in the extinction process or have documented the importance of gene flow in reversing population declines. This prompted one recent publication to declare that a revolution in conservation genetics has occurred. Contemporaneously with this revolution are a series of papers demonstrating long-term population persistence for several species despite having little or no detectable genetic variation. In a couple of notable cases, populations have been shown to have survived for centuries at small population size and with depleted levels of genetic variation. These contradictory results demand an explanation. In this review, I will show that these results do not necessarily fly in the face of theory as sometimes stated. The reconciliation of these two sets of observations relies on the incorporation of two major concepts. (1) Genetic factors do not act in a vacuum and it is their interaction with the environment, the strength and type of selection imposed, and the life history of the organism that determine the relative importance of genetic factors to extinction risk. (2) The relationship between molecular estimates of genetic variation and evolutionary potential, the relevance of genetic bottlenecks to adaptive genetic variation, and the nature of the stochastic process of extinction must be better integrated into expectations of population viability. Reports of populations persisting for hundreds of generations with very little detectable genetic variation provide us not only with valuable information but also with hope. However, recent studies suggest that we should not be sanguine about the importance of genetic diversity in the conservation of biodiversity. [source] Quantitative trait loci for porcine white blood cells and platelet-related traits in a White Duroc × Erhualian F2 resource populationANIMAL GENETICS, Issue 3 2009S. Yang Summary White blood cell count and platelets are implicated as risk factors for common complex diseases. Genetic factors substantially affect these traits in humans and mice. However, little is known about the genetic architecture of these traits in pigs. To identify quantitative trait loci (QTL) for leucocyte- and platelet-related traits in pigs, the total leucocyte number and differential leucocyte counts including the fraction of basophils, eosinophils, lymphocytes, monocytes, neutrophils, and a series of platelet parameters including platelet count, mean platelet volume, platelet distribution width and plateletcrit were measured in 1033 F2 animals on 240 days from a White Duroc × Erhualian intercross resource population. A total of 183 informative microsatellites distributed across 19 pig chromosomes (SSC) were genotyped across the entire resource population. Thirty-three QTL were identified for the examined traits, including eight genome-wide significant QTL for white blood cells and differential leucocyte counts on SSC2, 7, 8, 12 and 15 and six significant QTL for platelet-related traits on SSC2, 8, 13 and X. Erhualian or White Duroc alleles were not systematically associated with increased phenotypic values. These results not only confirmed many QTL identified previously in the mouse and swine, but also revealed a number of novel QTL for the traits recorded. Moreover, it is the first time that QTL for platelet-related traits in pigs have been reported. [source] Familial Aggregation and Heritability of Electrocardiographic Intervals and Heart Rate in a Rural Chinese PopulationANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009Jianping Li M.D., Ph.D. Background: Estimates of the genetic influences on electrocardiographic (ECG) parameters are inconsistent in previous reports, and no such studies have been performed in China. So we estimated genetic contributions to PR and QRS intervals and the rate-adjusted QT interval (Bazett's QTc) in a Chinese rural population. Methods: A total of 2909 subjects from 847 families were enrolled in the current study. Genetic contributions to ECG parameters were estimated in two ways: correlation coefficients among family members (father-mother, parent-offspring, first sibling-other sibling) and the heritability of each of the ECG parameters. Results: Our results showed significant correlations among family members on theses parameters: the correlation coefficients for PR interval, QRS duration, QTc interval, and HR, between parent-sibling, and sibling-sibling were 0.17 and 0.13, 0.18 and 0.23, 0.22 and 0.28, 0.19 and 0.18, respectively. The heritability for PR interval, QRS duration, QTc interval, and HR were estimated as 0.34, 0.43, 0.40, and 0.34, respectively. Conclusion: Genetic factors, together with the environmental and other cofactors contribute no more than 60% to the variance of the ECG intervals, supporting the concept that multiple factors, including gene-gene and gene-environment interactions could influence ECG interval phenotypes, and genetic factors play a major role. [source] Passively acquired anti-SSA/Ro antibodies are required for congenital heart block following ovodonation but maternal genes are notARTHRITIS & RHEUMATISM, Issue 10 2010Antonio Brucato Anti-SSA/Ro antibodies are necessary but not sufficient to provoke autoimmune-associated congenital heart block (CHB). Genetic factors are likely contributory. Accordingly, HLA-related candidates and single-nucleotide polymorphisms in the promoter region of tumor necrosis factor , and codon 10 in transforming growth factor ,1 (TGF,1) were evaluated in a unique family: the surrogate mother (anti-SSA/Ro positive), the biologic father, and the CHB-affected child (product of ovodonation). There was an HLA mismatch between the affected child and the surrogate mother. However, both the biologic and the surrogate mothers shared DQ2 and the profibrosing leucine polymorphism at codon 10 of TGF,. In conclusion, we observed that CHB can develop in a genetically unrelated child exposed in utero to anti-SSA/Ro antibodies. Testing for anti-SSA/Ro antibodies might be considered in women undergoing artificial fertilization. It is possible that there is no direct association of maternal genes beyond a contributory role in generating the autoantibody. [source] Gene polymorphisms and prostate cancer: the evidenceBJU INTERNATIONAL, Issue 11 2009Seyed S. Dianat OBJECTIVE Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome,wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression. MATERIALS AND METHODS We performed a PubMed® search using several key words such as prostate cancer, names of important genes with critical function, and polymorphisms. Then, we reviewed retrieved articles as well as relevant articles from 1997 to 2009. RESULTS There are conflicting results of studies on some gene polymorphisms in association with prostate cancer. Most of the inconsistent results have been reported in studies investigating the vitamin D receptor gene polymorphism in association with prostate cancer. Genes related to angiogenesis and cell adhesion genes are more promising. Following results of future studies, the use of antibodies blocking over-expressed genes or proteins may be supported in patients with prostate cancer. CONCLUSIONS The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome-wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors. [source] Genetic factors involved in the development of Helicobacter pylori -related gastric cancerCANCER SCIENCE, Issue 11 2006Nobuyuki Hamajima Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL-1B (C-31T or tightly linked T-511C), and TNF-A (T-1031C and C-857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin-associated gene A (PTPN11 A/G at intron 3) and to T-cell responses (IL-2 T-330G and IL-13 C-1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well-documented risk factors. In past case-control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori -related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori -related or -unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori -related. In order to elucidate the genetic traits of H. pylori -related gastric cancer, stepwise evaluation will be required. (Cancer Sci 2006; 97: 1129,1138) [source] Schizophrenia: genetics, prevention and rehabilitationACTA NEUROPSYCHIATRICA, Issue 3 2009Paolo Olgiati Objective:, Genetic factors are largely implicated in predisposing to schizophrenia. Environmental factors contribute to the onset of the disorder in individuals at increased genetic risk. Cognitive deficits have emerged as endophenotypes and potential therapeutic targets for schizophrenia because of their association with functional outcome. The aims of this review were to analyse the joint effect of genetic and environmental (G×E) factors on liability to schizophrenia and to investigate relationships between genes and cognitive endophenotypes focusing on practical applications for prevention and rehabilitation. Methods:, Medline search of relevant studies published between 1990 and 2008. Results:, In schizophrenia, examples of G×E interaction include the catechol- O -methyl transferase (COMT) (Val158Met) polymorphism, which was found to moderate the onset of psychotic manifestations in response to stress and to increase the risk for psychosis related to cannabis use, and neurodevelopmental genes such as AKT1 (serine-threonine kinase), brain-derived neurotrophic factor (BDNF), DTNBP1 (dysbindin) and GRM3 (metabotropic glutamate receptor 3), which were associated with development of schizophrenia in adulthood after exposure to perinatal obstetric complications. Neurocognitive deficits are recognised as core features of schizophrenia that facilitate the onset of the disorder and have a great impact on functional outcome. Neurocognitive deficits are also endophenotypes that have been linked to a variety of genes [COMT, neuregulin (NRG1), BDNF, Disrupted-In-Schizophrenia 1 (DISC1) and dysbindin] conferring susceptibility to schizophrenia. Recently, it has emerged that cognitive improvement during rehabilitation therapy was under control of COMT (Val158Met) polymorphism. Conclusion:, This review could indicate a pivotal role of psychiatric genetics in prevention and rehabilitation of schizophrenic psychoses. [source] The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: an investigation in healthy Danish twinsCLINICAL ENDOCRINOLOGY, Issue 6 2009Wendy M. Van Der Deure Summary Introduction, Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3, untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective, In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analysed the underlying functional mechanism by performing mRNA stability measurements and analysed the effect of these variants on D1 activity. Methods, Serum thyroid measurements and genotypes of the D1-C785T and D1-A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1-transfected JEG3 cells. Results, Carriers of the D1-785T allele had 3·8% higher FT4 and 14·3% higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0·87% and 1·79%, respectively, of the variation in serum FT4 and rT3. The D1-A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild-type D1 and the two variants. Conclusion, The D1-C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated. [source] | ||||||||||||||||||||||||||||||||||||||||||||||