rs3135506

This study investigated gene-environment interactions between 23 GWAS-identified lipid-associated SNPs and serum vitamins A and E in the National Health and Nutrition Examination Surveys (NHANES), including 5,576 participants across three racial/ethnic groups. Nine significant interactions were identified, with the most significant being APOB rs693×vitamin E associated with LDL-C in Mexican Americans (p=8.94×10⁻⁷). These nine interactions explained only 0.35-1.28% of variation in lipid traits, suggesting that gene-environment interactions account for modest proportions of the missing heritability in lipid metabolism.

This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.

This longitudinal study of 4,554 participants from the Busselton Health Survey examined associations between four SNPs in APOA5, LPL, and GCK genes with glucose and lipid traits over time. Cross-sectional analyses confirmed that GCK rs1799884 was associated with fasting glucose (beta=0.01, p=0.003), APOA5 rs662799 and rs3135506 with triacylglycerol levels (p<0.0001), and LPL rs328 with reduced triacylglycerol and raised HDL-C. Longitudinal analyses (n=2,864) showed these genetic effects on lipid and glucose traits remain stable with age during adulthood.

This review examines 15 years of ischemic stroke susceptibility gene research, organized into three periods: early candidate gene studies (1985-1995) testing variants in hemostasis and homocysteine metabolism genes; expansion period with functional variants discovered from other diseases tested on larger stroke cohorts; and current GWAS-driven large-scale genotyping studies. Key findings include identification of susceptibility loci in CELSR1 (rs6007897, rs4044210 in Japanese populations), PITX2 (rs2200733, rs10033464), and other genes involved in lipid metabolism (APOA5, APOCIII, MLXIPL) and signal transduction (PDE4D, ALOX5AP), with evidence that alleles are often shared across diseases and that careful clinical stratification is critical.

In 1,073 men and 1,207 women from the Framingham Offspring Study, the APOA5 -1131T>C polymorphism showed a significant gene-diet interaction with total fat intake in determining BMI and obesity risk (OR=0.61, 95% CI=0.39-0.98 for obesity in high-fat consumers). Carriers of the -1131C minor allele showed no increase in BMI with higher fat intake, while TT homozygotes showed increased BMI with increasing fat intake. The 56C>G (S19W) polymorphism did not show this interaction.