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Common Polymorphisms (common + polymorphism)

Distribution by Scientific Domains

Medical Sciences	78%
Life Sciences	21%

Distribution within Medical Sciences

Dermatology	11%
Geriatric Medicine	7%

Selected Abstracts

Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis

EXPERIMENTAL DERMATOLOGY, Issue 9 2009
Wolfgang Weger
Abstract Background:, Psoriasis is a chronic inflammatory skin disease. Among other cytokines, interleukin 22 (IL-22) has been implicated in the pathogenesis of chronic plaque psoriasis. The purpose of this study was to investigate a hypothesized association between common IL-22 gene polymorphisms and chronic plaque psoriasis. Methods:, Genotypes of 10 common polymorphisms of the IL-22 gene were determined by fluorogenic 5, exonuclease assays (TaqMan) in 475 patients with chronic plaque psoriasis and 252 controls. Results:, Two blocks of high linkage disequilibrium, formed by eight polymorphisms upstream of exon 5 (rs2227485, rs2227491, rs2046068, rs1179251, rs1012356, rs2227501, rs2227503, rs976748) and two polymorphisms in the 3, near gene region (rs1182844, rs1179246), were observed within the IL-22 gene. Neither single polymorphisms nor haplotypes were significantly associated with the presence or clinical features of chronic plaque psoriasis (P > 0.05). Conclusions:, Our data suggest that the investigated IL-22 gene polymorphisms are unlikely major risk factors for chronic plaque psoriasis. [source]

Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopy

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2000
A. Heinzmann
Recently, a linkage of the chromosomal region 19q13.4 with bronchial asthma has been demonstrated. This region harbours the so-called leucocyte receptor cluster with the gene for immunoglobulin-like-transcript 3 (ILT3) as a member. ILT3 represents an inhibitory receptor bearing three immunoreceptor tyrosine inhibitory motifs (ITIM). The protein mediates downregulation of cell activation through recruitment of different SH2-containing protein tyrosine phosphatases. With regard to the negative immunoregulatory function particularly on B-cells, ILT3 represents a candidate gene for atopy and asthma. The aim of this study was to screen for common polymorphisms in the gene coding for ILT3 and to test for association with the atopic phenotype. Using single-stranded conformal polymorphism-analysis and direct genomic sequencing seven polymorphisms, three mutations, a common deletion of 7 bp in the third intron and evidence for further alternative splicing of the ILT3 gene were found. Although no association was found with atopy phenotypes, it might prove useful to test for association with bronchial asthma. [source]

A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009
J. Genuneit
Summary Background Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case,control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. Methods We compared 1105 wheezing and 3137 non-wheezing children aged 8,12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. Results Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. Conclusions Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema. [source]

Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010
Kenneth D. Gadow
Abstract The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (,p2) was used to gauge the magnitude of group differences: 0.01,0.06 = small, 0.06,0.14 = moderate and > 0.14 = large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (,p2 = 0.10) and teachers' (,p2 = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (,p2 = 0.07) and obsessions,compulsions (,p2 = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ,p2 = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples. [source]

Analysis of growth hormone receptor polymorphism in Japanese semisuper centenarians

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2006
Yuchen Du
Background: Recent studies have demonstrated a significant association between mutations in genes involved in the GHR/IGF1 signaling pathway and extension of the lifespan of model organisms. Exon 3 insertion or deletion is one common polymorphism in the growth hormone receptor (GHR) of humans. The exon 3 deletion allele is reported to have stronger signaling in the GH/GHR pathway, which may correlate to short lifespan. Methods: We investigated the common polymorphic variation in 119 Japanese semisuper centenarians (SSC; older than 105) compared with 104 healthy younger controls via the polymorphism-based polymerase chain reaction method. Results: The frequency of exon 3 deletion variation of GHR in SSC was found to be higher than controls, although this was not significant statistically. Also, the single nucleotide polymorphism genotype frequency and allele frequency exhibited no differences between SSC and controls. Conclusions: These results show that SSC in Japan do not tend to have the allele of GHR, which has a lower signaling capacity. [source]

Lack of association between the G-2548A polymorphism of the leptin gene and psoriasis in a Turkish population

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2007
Nurten Kara PhD
Background,, Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T-helper response. A common polymorphism in the promoter of the human leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis. Aim, To investigate the association between psoriasis and leptin gene polymorphism (G-2548A). Methods, The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The frequencies of alleles and genotypes in patients and controls were compared. The relationship between leptin gene polymorphism and the clinical features of the patients was analyzed. Results, Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501,1.694; P = 0.792] and allele (OR, 0.864; 95% CI, 0.600,1.242; P = 0.429) frequencies were not significantly different between patient and control groups. In addition, there was no significant association between genotype and allele frequencies and the clinical characteristics of psoriasis. Conclusion, In this case,control study, no evidence of association between the G-2548A variant of the leptin gene and psoriasis was found. [source]

Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2001
TOMOYUKI KUBOTA M.D.
Ion Channel Polymorphism and Cardiac Arrhythmia. Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in , 11% of the Japanese population. This 1727G> A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S- KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT- KCNQ1 and G643S- KCNQ1 with KCNE1 resulted in , 30% reduction in the slow delayed rectifier K+ current IKs without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild IKs dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population. [source]

Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men

JOURNAL OF INTERNAL MEDICINE, Issue 6 2003
J. Skogsberg
Abstract. Objectives., Peroxisome proliferator activated receptor delta (PPARD) is a transcription factor implicated in the regulation of genes involved in cholesterol metabolism. We recently discovered a common polymorphism in the 5,-untranslated region (5,-UTR) of the human PPARD, +294T/C, that is associated with an increased plasma low-density lipoprotein cholesterol (LDL-C) concentration in healthy subjects. Whether the +294C allele is associated with LDL-C elevation independently of the background lipoprotein phenotype and whether it confers increased risk of coronary heart disease (CHD) is unknown. Against this background, we investigated the relationships between the PPARD polymorphism and plasma lipoprotein concentrations and the risk for contracting CHD in the West of Scotland Coronary Prevention Study (WOSCOPS). Design., A nested case,control study of participants in a randomized double-blind placebo-controlled trial of pravastatin in mildly-to-moderately hypercholesterolaemic men. Subjects., A total of 580 cases of incident CHD and 1160 individuals who remained free of CHD (controls). Main outcome measures., Plasma lipoprotein con-centrations and risk of CHD according to PPARD genotype. Results., Individuals carrying the rare PPARD +294C allele had a significantly lower high-density lipoprotein cholesterol (HDL-C) concentration than subjects homozygous for the common T-allele. Homozygous carriers of the C-allele also showed a tendency towards higher risk of CHD compared with homozygous carriers of the T-allele. In addition, a gene,gene interaction involving the PPARD polymorphism and the PPAR alpha L162V polymorphism may influence the plasma LDL-C concentration. Conclusions., PPARD plays a role in cholesterol metabolism in man. [source]

Inversion of the Williams syndrome region is a common polymorphism found more frequently in parents of children with Williams syndrome,

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2010
Holly H. Hobart
Abstract Williams syndrome (WS) is a multisystem disorder caused by deletion of about 1.55,Mb of DNA (including 26 genes) on chromosome 7q11.23, a region predisposed to recombination due to its genomic structure. Deletion of the Williams syndrome chromosome region (WSCR) occurs sporadically. To better define chance for familial recurrence and to investigate the prevalence of genomic rearrangements of the region, 257 children with WS and their parents were studied. We determined deletion size in probands by metaphase FISH, parent-of-origin of the deleted chromosome by molecular genetic methods, and inversion status of the WSCR in both parents by interphase FISH. The frequency of WSCR inversion in the transmitting parent group was 24.9%. In contrast, the rate of inversion in the non-transmitting parent group (a reasonable estimate of the rate in the general population) was 5.8%. There were no significant gender differences with respect to parent-of-origin for the deleted chromosome or the incidence of the inversion polymorphism. There was no difference in the rate of spontaneous abortion for mothers heterozygous for the WSCR inversion relative to mothers without the inversion. We calculate that for a parent heterozygous for a WSCR inversion, the chance to have a child with WS is about 1 in 1,750, in contrast to the 1 in 9,500 chance for a parent without an inversion. © 2010 Wiley-Liss, Inc. [source]

Effect of the APOE-491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 5 2002
G. Roks
Abstract The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this ,491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population-based case-control study. We found that there was a modest but statistically significant effect of the ,491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the ,491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the ,491A/T polymorphism has an APOE genotype-independent effect on plasma apolipoprotein E levels but no APOE-independent effect on AD risk. © 2002 Wiley-Liss, Inc. [source]

Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson's disease

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010
L. Gao
Gao L, Díaz-Corrales FJ, Carrillo F, Díaz-Martín J, Caceres-Redondo MT, Carballo M, Palomino A, López-Barneo J, Mir P. Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson's disease. Acta Neurol Scand: 2010: 122: 41,45. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives,, Parkinson's disease (PD) is characterized by the dopaminergic neuronal death in substantia nigra, and genetic factors appear to be involved in the pathophysiology of this disease. Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and is necessary for the survival of dopaminergic neurons in substantia nigra. G196A, a common polymorphism of the BDNF gene, not only affects cognitive and motor processes, but also is associated with various psychiatric disorders. We evaluated whether G196A polymorphism is associated with PD and/or modifies clinical manifestations in PD patients. Methods,, We included 193 PD patients and 300 control subjects. G196A polymorphism was screened by restriction fragment length polymorphism analysis. Clinical features of each patient were examined in detail. The possible association between genotype and clinical characteristics were determined by bivariate and multivariate analyses. Results,, The distribution of G196A allele and genotype frequency was similar between PD and control subjects. Clinical characteristics, including Hoehn-Yahr stage, motor symptoms, non-motor symptoms (depression, cognitive dysfunction, psychiatric dysfunctions, and sleep behavior disorder), and dyskinesias, were not associated with this polymorphism. Conclusions,, G196A polymorphism is not a risk factor for PD and does not seem to modify clinical features in PD patients studied here. [source]

Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetes

DIABETIC MEDICINE, Issue 8 2008
D. Currie
Abstract Aims Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. Methods Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. Results ,2 analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case,control collection negated this association. Conclusions We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes. [source]

Maternal transmission of diabetes

DIABETIC MEDICINE, Issue 2 2002
J. C. Alcolado
Abstract Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNAleu(UUR) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune ,-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena. [source]

Genetic variation for dorsal,ventral patterning of the Drosophila melanogaster eggshell

EVOLUTION AND DEVELOPMENT, Issue 2 2005
Lisa M. Goering
Summary Patterning of the insect eggshell is an excellent system for exploring the molecular basis of phenotypic variation. In Drosophila melanogaster, two dorsal,anterior respiratory appendages are produced in response to signaling through the Epidermal growth factor receptor (Egfr). Previous work implicates Egfr pathway function in both intraspecific variation for dorsal appendage spacing (DAS) on the eggshell, as well as interspecific differences in dorsal appendage number and location. To test the hypothesis that genetic variation in Egfr contributes to variation in eggshell patterning, we have made use of naturally occurring intraspecific variation for DAS as a model quantitative trait. We found that there is substantial segregating genetic variation for DAS in D. melanogaster, and have tested for associations with 289 common polymorphisms in the Egfr locus. A marginal association was seen with two polymorphic sites in Egfr; however, we failed to replicate these findings in a second population, or in a modified quantitative complementation test designed to specifically test the effects of the putative polymorphisms. Therefore, we conclude that the polymorphisms we have identified in Egfr do not contribute to variation in DAS, and further work is required to understand the genetic architecture of this trait. [source]

Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis

Summary of contributions to GAW Group 15: family-based samples are useful in identifying common polymorphisms associated with complex traits

GENETIC EPIDEMIOLOGY, Issue S1 2009
Stacey Knight
Abstract Traditionally, family-based samples have been used for genetic analyses of single-gene traits caused by rare but highly penetrant risk variants. The utility of family-based genetic data for analyzing common complex traits is unclear and contains numerous challenges. To assess the utility as well as to address these challenges, members of Genetic Analysis Workshop 16 Group 15 analyzed Framingham Heart Study data using family-based designs ranging from parent,offspring trios to large pedigrees. We investigated different methods including traditional linkage tests, family-based association tests, and population-based tests that correct for relatedness between subjects, and tests to detect parent-of-origin effects. The analyses presented an assortment of positive findings. One contribution found increased power to detect epistatic effects through linkage using ascertainment of sibships based on extreme quantitative values or presence of disease associated with the quantitative value. Another contribution found four single-nucleotide polymorphisms (SNPs) showing a maternal effect, two SNPs with an imprinting effect, and one SNP having both effects on a binary high blood pressure trait. Finally, three contributions illustrated the advantage of using population-based methods to detect association to complex binary or quantitative traits. Our findings highlight the contribution of family-based samples to the genetic dissection of complex traits. Genet. Epidemiol. 33 (Suppl. 1):S99,S104, 2009. © 2009 Wiley-Liss, Inc. [source]

Screening of 25 Italian patients with Niemann-Pick a reveals fourteen new mutations, one common and thirteen private, in SMPD1,,

HUMAN MUTATION, Issue 1 2004
V. Ricci
Abstract Niemann-Pick disease (NPD) results from the deficiency of lysosomal acid sphingomyelinase (SMPD1). To date, out of more than 70-disease associated alleles only a few of them have a significant frequency in various ethnic groups. In contrast, the remainder of the mutations are rare or private. In this paper we report the molecular characterization of an Italian series consisting of twenty-five NPD patients with the severe neurodegenerative A phenotype. Mutation detection identified a total of nineteen different mutations, including 14 novel mutations and five previously reported lesions. The known p.P189fs and the novel p.T542fs were the most frequent mutations accounting for 34% and 18% of the alleles, respectively. Screening the alleles for the three common polymorphisms revealed the variant c.1516G>A (exon 6) and the repeat in exon 1, but not the variant c.965C>T (exon 2). In absence of frequent mutations, the prognostic value of genotyping is limited. However, new genotype/phenotype correlations were observed for this disorder that could in the future facilitate genetic counseling and guide selection of patients for therapy. © 2004 Wiley-Liss, Inc. [source]

A search for cyclophilin-A gene (PPIA) variation and its contribution to the risk of atherosclerosis and myocardial infarction

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2008
M. Palacín
Summary Cyclophilin A is secreted by vascular smooth muscle cells in response to inflammatory stimuli, and could thus contribute to atherosclerosis. We hypothesized that the genetic variation at the cyclophilin A gene (PPIA) could affect the risk for developing atherosclerosis and myocardial infarction. This study included 250 myocardial infarction patients (all male and < 60 years; 95% are smokers). All these cases had at least one atherosclerotic diseased coronary vessel. DNA was obtained from patients and from 250 healthy controls. The variation at the PPIA gene was determined in the patients through single-strand conformation analysis and direct sequencing of seven polymerase chain reaction fragments. Allele and genotype frequencies were compared between patients and controls. The effect of a promoter polymorphism (,11 G/C) on gene expression was in vitro analysed with luciferase-reporter assays. We found two common polymorphisms in the PPIA promoter (,11 G/C) and the 5, non-translated (+36 G/A) regions. Cells transfected with luciferase-plasmids containing the ,11 G had significantly higher luciferase activity. Genotype frequencies for these polymorphisms did not differ between patients and controls. In conclusion, we reported a functional variant in the PPIA promoter. However, the PPIA variation did not significantly contribute to the risk of suffering from myocardial infarction among patients with atherosclerotic diseased vessels. [source]

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2004
G. Latkovskis
Summary C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1,, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(,511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(,174) and IL-6(,572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311,0.574) for CT or TT genotypes compared with 0.240 (0.107,0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l,1, respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115,0.388) for carriers and 0.421 (0.290,0.552) for non-carriers (CRP 1.79 and 2.64 mg l,1, respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients. [source]

Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopy

Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline

IUBMB LIFE, Issue 6 2007
Steven H. Zeisel
Abstract Recent progress in the understanding of the human dietary requirement for choline highlights the importance of genetic variation and epigenetics in human nutrient requirements. Choline is a major dietary source of methyl-groups (one of choline's metabolites, betaine, participates in the methylation of homocysteine to form methionine); also choline is needed for the biosynthesis of cell membranes, bioactive phospholipids and the neurotransmitter acetylcholine. A recommended dietary intake for choline in humans was set in 1998, and a portion of the choline requirement can be met via endogenous de novo synthesis of phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT) in the liver. Though many foods contain choline, many humans do not get enough in their diets. When deprived of dietary choline, most adult men and postmenopausal women developed signs of organ dysfunction (fatty liver, liver or muscle cell damage, and reduces the capacity to handle a methionine load, resulting in elevated homocysteine). However, only a portion of premenopausal women developed such problems. The difference in requirement occurs because estrogen induces expression of the PEMT gene and allows premenopausal women to make more of their needed choline endogenously. In addition, there is significant variation in the dietary requirement for choline that can be explained by common polymorphisms in genes of choline and folate metabolism. Choline is critical during fetal development, when it alters DNA methylation and thereby influences neural precursor cell proliferation and apoptosis. This results in long term alterations in brain structure and function, specifically memory function. IUBMB Life, 59: 380 - 387, 2007 [source]

Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias

Paraoxonase 1 activities and polymorphisms in autism spectrum disorders

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2010
Sergiu P. Pa
Abstract Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of conditions of unknown aetiology, characterized by significant disturbances in social, communicative and behavioural functioning. Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype. [source]

Personalized nutrition for the prevention of cardiovascular disease: a future perspective

JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2008
J. A. Lovegrove
Abstract Cardiovascular disease (CVD) is responsible for significant morbidity and mortality in the Western and developing world. This multi-factorial disease is influenced by many environmental and genetic factors. At present, public health advice involves prescribed population-based recommendations, which have been largely unsuccessful in reducing CVD risk. This is, in part, due to individual variability in response to dietary manipulations, that arises from nutrient,gene interactions (defined by the term ,nutrigenetics'). The shift towards personalized nutritional advice is a very attractive proposition, where, in principle, an individual can be given dietary advice specifically tailored to their genotype. However, the evidence-base for the impact of interactions between nutrients and fixed genetic variants on biomarkers of CVD risk is still very limited. This paper reviews the evidence for interactions between dietary fat and two common polymorphisms in the apolipoprotein E and peroxisome proliferator-activated receptor-, genes. Although an increased understanding of how these and other genes influence response to nutrients should facilitate the progression of personalized nutrition, the ethical issues surrounding its routine use need careful consideration. [source]

A Functional Polymorphism of the NFKB1 Gene Increases the Risk for Alcoholic Liver Cirrhosis in Patients With Alcohol Dependence

ALCOHOLISM, Issue 11 2009
Miguel Marcos
Background:, The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-,B, the NF-,B inhibitor , (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-, in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC. Methods:, A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the ,94ins/delATTG NFKB1, 3,-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance. Results:, We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC. Conclusions:, The deletion allele of the ,94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data. [source]

Methylenetetrahydrofolate Reductase Polymorphisms, Folate, and Cancer Risk: A Paradigm of Gene-Nutrient Interactions in Carcinogenesis

NUTRITION REVIEWS, Issue 7 2000
F.R.C.P.(C), Young-In Kim M.D.
Recent epidemiologic studies suggest that common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in the general North American population may modulate cancer risk. In some cancers, folate and other nutrients involved in the MTHFR metabolic pathway appear to interact with MTHFR polymorphisms to further modify cancer risk. In carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient interactions, an emerging and important topic in the field ofnutritisn and cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide an opportunity to identify an ideal target group of individuals, at high risk of developing cancer, for rational, effective, and safe chemoprevention using these nutrients. [source]

Lack of genetic association between cholesteryl ester transfer protein and Japanese sporadic Alzheimer's disease

PSYCHOGERIATRICS, Issue 4 2006
Akiyoshi KITAJIMA
Abstract Background:, Cholesteryl ester transfer protein regulates the plasma high density lipoprotein cholesterol level, which is considered to play an antiatherogenic role in humans. The presence of apolipoprotein E epsilon4 allele is a strong risk factor for developing Alzheimer's disease (AD). Since apolipoprotein E is a regulator of lipid metabolism, it is reasonable to assume that lipids play important roles in the pathogenesis of AD. Methods:, We studied the relationship between polymorphisms of the cholesteryl ester transfer protein gene and risk for AD, analyzing two common polymorphisms of the gene and the relationship between them and plasma cholesterol level control samples. Results:, These polymorphisms showed no association with risk for AD. In rs5882, there was no significant difference in the mean plasma cholesterol concentrations found between patients with the A/A, A/G and G/G genotype. For rs2303790, no significant difference in the mean baseline cholesterol concentrations was found between patients with the A/A genotype and carriers of the G allele. Conclusion:, Our study indicates that these polymorphisms, rs5882 and rs2303790 were not associated with risk for AD. We also pointed out that these two polymorphisms do not affect plasma cholesterol levels in our Japanese AD samples. [source]

Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancer

THE PROSTATE, Issue 2 2004
Fredrik Lindmark
Abstract BACKGROUND The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5,- or 3,-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P,=,0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology. © 2004 Wiley-Liss, Inc. [source]

A-G-4G haplotype of PAI-1 gene polymorphisms ,844 G/A, HindIII G/C, and ,675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
M. G. Adamski
Background,,, Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (,844 G/A, ,675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. Methods,,, We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. Results,,, A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions,,, Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of ,844 G/A, ,675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke. [source]

Sex-specific association between leptin receptor polymorphisms and leptin levels and BMI in healthy adolescents,

ACTA PAEDIATRICA, Issue 10 2010
P Riestra
Abstract Aim:, To examine the relationship of three common polymorphisms in the leptin receptor (LEPR) gene, implicated in the regulation of body weight, with leptin levels and obesity-related phenotypes in a population-based sample of healthy pubertal children in Spain. Methods:, The study included 806 boys and girls aged 12,16 whose anthropometrical data and body composition were recorded. Serum leptin levels were determined by ELISA. The LEPR Q223R, K109R and K656N polymorphisms were determined by TaqMan® allelic discrimination assays. Results:, When analysing the Q223R polymorphism, we observed that female carriers of the RR genotype had significantly higher plasma leptin levels (18.2 vs. 15.1 ng/mL p = 0.016) and significantly higher mean BMI values (22.5 vs. 21.3 Kg/m2 p = 0.032) than QR carriers. Furthermore, the frequency of the RR genotype in overweight-obese girls was significantly higher than that found in normal-weight girls. No significant differences were observed in boys. Neither boys nor girls showed significant differences when comparing leptin levels, anthropometric variables or body composition by K109R or K656N genotype. Conclusion:, The fact, that the Q223R polymorphism in the LEPR gene is significantly associated with leptin levels and BMI only in girls, suggests a sex-specific influence of this polymorphism on these variables. [source]