Analysis of association of apolipoprotein genes APOA2, APOA5 and APOH variants with hyperlipidemia

Abstract

Hyperlipidemia is one of the most common metabolic disorders in humans, leading to the atheros clerosis. It is known that lipid metabolism disorders can be associated with genetic predisposition. However, even in patients with clinically confirmed familial hypercholesterolemia, its genetic cause remains unknown in 30 % of cases. The search for genetic variants associated with primary hyperlipidemias is a promising direction in the development of diagnostics and personalized medicine. Aim of the study was to assess of the association of polymorphic sites rs3813627, rs3135506 and rs3785617 of the apolipoprotein genes APOA2, APOA5 and APOH, respectively, with lipid metabolism and atherogenic index in the population of Novosibirsk. Material and methods. Genotyping by polymerase chain reaction followed by analysis of restriction fragment length polymorphism at the rs3813627, rs3135506 and rs3785617 of the APOA2, APOA5 and APOH genes, respectively, was carried out in 522 people from 9360 a random population sample of Novosibirsk and in 266 people from the same sample with a total cholesterol content more than 300 mg/dl. A one-way ANOVA of the association of genetic variants with serum lipid levels and atherogenicity index was performed. Results. The allele frequencies of all studied polymorphic sites in the Novosibirsk population differed from those previously identified among Europeans. A significant increase (p = 0.02) in average total cholesterol content in AA – AG – GG genotype series for rs3785617 of the APOH was revealed. The frequency of the CC genotype for the rs3135506 of the APOA5 in the group with total cholesterol contentration exceeding 300 mg/dl was lower compared to the control group (p = 0.038, odds ratio 0.66, 95 % confidence interval 0.46–0.97). For rs3813627, there were no differences in genotype frequencies and in lipid metabolism. Conclusions. The rs3135506 and rs3785617 can modify the hyperlipidemia phenotype among the Caucasoid population of Western Siberia.