Evaluation of the gene-age interactions in HDL cholesterol, LDL cholesterol, and triglyceride levels: the impact of the SORT1 polymorphism on LDL cholesterol levels is age dependent.

Several genes that influence HDL-C, LDL-C, and triglyceride levels have been identified. The effects of genetic polymorphisms on lipid levels may be age dependent. We replicated 17 of these previously identified associations and then used cross-sectional and longitudinal analysis to investigate age-SNP interaction effects. The rs646776 SNP at the SORT1 locus showed an age interaction that was significant in cross-sectional analyses of 1350 individuals from Utah (p = 0.0003) and in 2977 individuals from the NHLBI Family Heart Study (p = 0.007) as well as in longitudinal analysis of a subsample of 1099 individuals from the Utah cohort that had been followed for over 20 years (p = 0.0001). The rs646776 genotype-specific difference in LDL-C levels was significantly greater for younger individuals than for older individuals. These findings may help elucidate the mode of action of the SORT1 gene and impact potential therapeutic interventions targeting this pathway.