The Protective Effect of Polymorphisms rs2681472 and rs17249754 of the ATP2B1 Gene Against Coronary Artery Disease and Hypertension is Abolished by Tobacco Smoking

Abstract

Aim    To study the relationship of single nucleotide polymorphisms rs2681472 and rs17249754 in the ATP2B1 gene with risk of ischemic heart disease (IHD) and arterial hypertension (AH) among residents of Central Russia and to evaluate the trigger role of smoking as a risk factor for development of IHD and AH in carriers of ATP2B1 gene polymorphic variants.Material and methods    The study included DNA samples from 1960 residents of Central Russia of Slavic origin. Among them, there were 1261 patients with cardiovascular diseases and 699 healthy persons. The vast majority of patients had both IHD and AH. Genotyping was performed using the iPLEX technique on a MassARRAY-4 genomic mass-spectrometer. The relationship of ATP2B1 alleles, genotypes, and haplotypes with the risk of diseases was calculated by logistic regression analysis with adjustments for sex and age.Results    Carriage of AG and GG (rs2681472) genotypes and GA (rs17249754) genotype was associated with a reduced risk of both IHD (p=0.0057 and p=0.022 for rs2681472 and rs17249754, respectively) and AH (p=0.016 and p=0.036, respectively). Rare rs2681472G-rs17249754G and rs2681472A-rs17249754A haplotypes were associated with a reduced risk of IHD (odds ratio, OR, 0.22; 95 % CI: 0.11–0.46, p=0.0001) and AH (OR, 0.22; 95 % CI: 0.10–0.47, p=0.0001). Analysis of the groups stratified by the smoking status showed that in smokers, the studied polymorphic variants did not have a protective action with respect of either IHD or AH. However, in non-smokers, the genotypes AG and GG rs2681472 (OR, 0.62; 95 % CI: 0.47–0.80, p=0.0004) and GA rs17249754 (OR, 0.61; 95 % CI: 0.47–0.81, p=0.0004) were associated with a reduced risk of IHD and AH (OR, 0.63; 95 % CI: 0.48–0.83, p=0.0004 for rs2681472; OR, 0.63; 95 % CI: 0.48–0.83, p=0.001 for rs17249754), as well as the carriage of the minor alleles rs2681472‑G and rs17249754‑A.Conclusion    It was shown for the first time that the polymorphic variants rs17249754 and rs2681472 of the ATP2B1 gene are associated with a reduced risk for IHD and AH only in non-smokers.