Single nucleotide polymorphisms in genes encoding xenobiotic metabolizing enzymes are associated with predisposition to arterial hypertension
Background: Arterial hypertension (AH) is the most common disease of the cardiovascular system. Intracellular chemical and oxidative stress, which can be associated both with direct exposure to toxic xenobiotics and with their excessive activation during biotransformation, may lead to endothelial dysfunction and increased risk of AH development. The aim of the study: To investigate the association of single nucleotide polymorphisms of genes involved in the biotransformation of xenobiotics (rs1048943 CYP1A1, rs762551 CYP1A2, rs1056836 CYP1B1, rs1799930 NAT2, rs1800566 NQO1, rs11045642 MDR1) with predisposition to arterial hypertension. Materials and methods: A total of 702 patients with AH (307 men, 395 women; mean age 55 years) and 857 gender- and age- matched relatively healthy volunteers (406 men, 451 women; mean age 53 years) were recruited for the study. Genotyping of SNPs were done using TaqMan-based PCR. Results: Comparative analysis of genotype frequencies (log-additive regression model was used, all calculations were performed with adjustment for gender, age) showed that SNP rs762551 CYP1A2 was associated with a decreased risk of AH (ORadj=0.85, 95%CIadj=0.73-0.99; Padj=0.038); SNP rs1045642 MDR1 (ABCB1) was associated with an increased risk of AH (ORadj=1.20, 95% CIadj=1.04-1.39; Padj=0.013). Moreover, SNP rs762551 CYP1A2 was associated with the age of manifestation of arterial hypertension (Differenceadj=1.51; 95%CIadj=0.22-2.80) and cholesterol level (Differenceadj= -0.15; 95% Cladj = -0.29 - -0.01). Conclusion: Thus, in this study, for the first time, there was found the association of rs762551 CYP1A2 and rs1045642 ABCB1 (MDR1) with arterial hypertension in Russians.