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Important Genetic Determinant (important + genetic_determinant)
Selected AbstractsGenetic variation in D7S1875 repeat polymorphism of leptin gene is associated with increased risk for depression: a case-control study from IndiaDEPRESSION AND ANXIETY, Issue 9 2009Manav Kapoor M.Sc. Abstract Background: Epidemiologic data suggest an association between obesity and depression, however findings vary considerably across different studies. Both depression and obesity are disabling disorders associated with loss over appetite control, influenced by genetic and environmental factors and are risk factors for diseases like hypertension, cardiovascular disorders, etc. This study attempts to establish a link between the symptoms of depression, metabolic disorders, and obesity, to unravel the underlying association/s. Methods: This exploratory case,control study comprises 133 clinically diagnosed depressed individuals and 136 age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain reaction. Results: Frequency of the shorter allele of D7S1875 (<208,bp) was 0.73 in the depressive group versus 0.67 in the control group (P=.01). Cases homozygous for D7S1875,208,bp alleles had significantly higher value of systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood pressure (SBP and DBP) than the individuals homozygous for<208,bp allele. A similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be an important genetic determinant for susceptibility to depression in the Indian population (OR=1.4913, 95% CI=1.0334,2.1522; P=.04). Conclusions: Our findings suggest that LEP gene variants could be related to depression and associated co-morbidities such as hypertension. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [source] A recombined haplotype in the major histocompatibility region contains a cluster of genes conferring high susceptibility to ulcerative colitis in the Spanish populationINFLAMMATORY BOWEL DISEASES, Issue 9 2005Laura Fernández PhD Abstract Background: The most consistently described associations in ulcerative colitis (UC) have been with human leukocyte antigen (HLA) class II alleles. Our aim was to look for associations among distinct genetic polymorphisms in the major histocompatibility complex (MHC) that might play a role in determining the susceptibility to UC and especially to the extensive form of the disease. Methods: A case-control study was performed with a total of 253 patients with UC and 315 healthy controls recruited from a single Spanish center. All the samples and 4 cell lines carrying DRB1*0103 or DRB1*1501 alleles were typed for the HLA-DRB1 class II gene and for a panel of HLA class III markers (D6S273, BAT_2, TNFa, b, c, d, e, IKBL+738, MICA). Results: The frequency of the alleles DRB1*0103, IKBL+738(C) (extending our previous results) and BAT_2-8 (newly typed) was increased in patients compared with controls (P = 0.00001, odds ratio [OR] = 5.90; P = 0.002, OR = 2.42; and P = 0.0001, OR = 3.04, respectively), and these associations were greatest in patients with extensive disease compared with patients with distal disease (P = 0.02, OR = 2.53; P = 0.002, OR = 3.06; and P = 0.03, OR = 2.08, respectively). The allelic combination DRB1*0103/D6S273-5/BAT_2-8/TNFa11b4c1d3e3/IKBL+738(C)/MICA5.1 that includes the telomeric class III markers of the 7.1 ancestral haplotype is highly increased in patients with UC (P = 0.0001, OR = 10.57), especially in those with the extensive form of the disease (P = 0.02, OR = 3.41 extensive versus distal). Conclusions: The above-mentioned pattern, most likely formed by recombination of the telomeric fragment of the MHC 7.1 ancestral haplotype, seems to be the most important genetic determinant of susceptibility to the extensive form of UC in our population. [source] The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interactionINFLAMMATORY BOWEL DISEASES, Issue 1 2005Marie Pierik MD Abstract Background and Aims: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-environment interaction (IBD4 × smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. Patients and Methods: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. Results: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P , 0.01; MAS 54.6%). MAS was higher in CD families in which all siblings or at least one sibling smoked compared with nonsmoking CD families (MAS, 58.90%, 57.50%, and 52.80%, respectively). Conclusions: The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for CD and also showed evidence for a gene-environment interaction at this locus. Further studies are needed to explore the mechanism by which smoking influences IBD4. [source] There is no evidence of an association in children and teenagers between the apolipoprotein E ,4 allele and post-traumatic brain swellingNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2004T. J. Quinn Traumatic brain injury (TBI) is an important cause of mortality and disability in children and teenagers. A particular feature of the neuropathology at post-mortem is brain swelling. The cause of the swelling in some cases is not known, while in others it is associated with traumatic axonal injury or hypoxia. Apolipoprotein E (APOE) ,4 allele is known to be an important genetic determinant of outcome in children after TBI. We hypothesized a relationship between possession of APOE,4 and diffuse traumatic brain swelling. A total of 165 cases aged between 2 and 19 years were identified from the department's tissue archive. APOE genotype was determined by polymerase chain reaction (PCR) in 106 cases. Bilateral swelling was present in 44 cases (11 with APOE,4), unilateral swelling in 25 cases (7 with APOE,4) and in 36 cases (9 with APOE,4) there was no evidence of brain swelling. There was no significant relationship between possession of APOE,4 and the presence of cerebral swelling (,2 = 0.09, df = 2, P = 0.96). The 95% confidence interval for difference in proportions with swelling, in, those, with, and, without, the,APOE,,4, is,,19%, to 22%. Thus, a significant relationship was not found between diffuse brain swelling and possession of APOE,4, and in this cohort of patients there was an identifying cause of the brain swelling in all cases. [source] The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma.CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2006The SAPALDIA Cohort Study Summary Background IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. Objective To examine the relationship of a genetic, haplotype-tagging promotor variant ,137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. Methods Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. Results The G-allele of the IL-18 promotor variant (,137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 ,137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64,8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66,1.94). The interaction between IL-18 ,137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. Conclusion Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma. [source] | ||||||||||