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Common Gene Variants (common + gene_variants)
Selected AbstractsHRAS1 and LASS1 with APOE are associated with human longevity and healthy agingAGING CELL, Issue 5 2010S. Michal Jazwinski Summary The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. [source] Testing Genetic Susceptibility Loci for Alcoholic Heart Muscle DiseaseALCOHOLISM, Issue 10 2001Olli A. Kajander Background: Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart. Methods: We studied 700 middle-aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid-phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase ,344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P-450 2E1 Dra I, Pst I, Rsa I, and Msp I. Results: The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes. Conclusions: The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease. [source] The influence of common gene variants of the xenobiotic receptor (PXR) in genetic susceptibility to intrahepatic cholestasis of pregnancyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010G. CASTAŅO Aliment Pharmacol Ther,31, 583,592 Summary Background, The xenobiotic nuclear pregnane X receptor is implicated in many physiological pathways and diseases, including bile acid detoxification and cholestasis. Aim, To estimate the contribution of common gene variants of the xenobiotic receptor (pregnane X receptor, PXR) to genetic susceptibility to intrahepatic cholestasis of pregnancy. Methods, A total of 101 intrahepatic cholestasis of pregnancy patients and 171 healthy pregnant women in the third trimester of their pregnancies were included. Four tag single nucleotide polymorphisms (SNPs) (rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3, with a minor allele frequency ,0.10 and representing 33 polymorphic sites were genotyped. Besides these, three additional SNPs (rs3814057, rs6785049, and rs7643645) were included because they showed previous evidence of functionality. Results, Genotypic test for single SNPs showed that rs2461823 genotypes were significantly associated with intrahepatic cholestasis of pregnancy (P < 0.0069), OR per G allele: 1.44, 95% CI: 1.01,2.05, P < 0.042. The Cochran-Armitage test for trend and the allelic test showed a significant association with disease status (P < 0.04 and 0.03 respectively), G being the risk allele. A positive association between rs2461823 and ALT, AST, and bilirubin concentrations was observed. Neonate birth weight adjusted by the Capurro index was significantly associated with rs2461823 (P < 0.05); the proportion of the total variation attributed to rs2461823 genotypes was 7.8%. Conclusion, Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy. [source] | ||||||||||