Associations of TOMM40 and APOE genes polymorphisms with quantitative phenotypes of cardiovascular system in Russian population of the Siberia region

Relevance: TOMM40 and APOE genes are located in the same locus on chromosome 19 (19p13). The analysis of a contribution of polymorphism in these genes to variability of clinically relevant quantitative traits in healthy individuals can evaluate their contribution to cardiovascular diseases. Purpose: to study 8 SNP polymorphisms and poly-T repeat in TOMM40/APOE locus in a sample of healthy individuals and to investigate associations of the polymorphisms with quantitative characteristics of cardiovascular system. Materials and methods: rs741780, rs2075650, rs1160985, rs157580, rs8106922, rs10524523 (poly-T repeat) in TOMM40 gene and APOE: rs7259620, rs429358, rs7412 were studied in the sample of individuals without cardiovascular diseases (Tomsk, N = 183 and Kemerovo, N = 183). Genotyping was carried out with real-time PCR and the fragment analysis. The analysis of associations with quantitative traits was performed by ANOVA or Mann-Whitney and Kraskel-Wallace’s nonparametric criteria. Results: In respect of allele frequencies Russian population of West Siberia is close to other Caucasian populations. Rare alleles of rs741780 and rs1160985 were associated with lower levels of triglycerides (p = 0,031 and p = 0,044, respectively); a long allele (L) of the poly-T repeat (rs10524523) was associated with higher glucose level (p = 0,027); rs7412 contributes to the variability of the total cholesterol level (p = 0.02) and low-density lipoprotein cholesterol (p = 0.06); rs2075650 was associated with systolic blood pressure and low-density lipoprotein cholesterol in males (p = 0,026 and p = 0,002); GG genotype of the rs8106922 was associated with triglycerides in females (p = 0,036); rs429358 was associated with the total cholesterol and low-density lipoprotein cholesterol (p = 0,002 and p = 0,006). Conclusions: Polymorphisms in TOMM40/APOE locus contribute to the variability of lipid parameters, glucose level, and arterial blood pressure in Russian inhabitants of Western Siberia.

популяция, сердечно-сосудистая система, липидный профиль, TOMM40, APOE, population, cardiovascular system, lipid profile, TOMM40, APOE

1. Пузырёв ВП. Вопросы вокруг идентифицируемых генов подверженности распространенным болезням человека. Молекулярно-биологические технологии в медицинской практике. 2009;13:3-16.

2. Aulchenko YS, Ripatti S, Lindqvist I et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet. 2009;41:47-55.

3. Middelberg RP, Ferreira MA, Henders AK et al. Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits. BMC Med Genet. 2011;12:123.

4. Talmud PJ, Drenos F, Shah S et al. Gene-centric Association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Am J Hum Genet. 2009;85:628-642.

5. The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature;526:68-74.

6. Roses AD, Lutz MW, Amrine-Madsen H, et al. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer’s disease. Pharmacogenomics Journal. 2010;10(5):375-384.

7. Ronald J, Rajagopalan R, Ranchalis JE et al. Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease. Lipids. Health. Dis. 2009;8:52.

8. Mazzotti DR, Singulane CC, Ota VK et al. Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort. Gene. 2014;535(2):370-375.