The purpose of this study was to investigate whether polymorphisms in genes involving aryl hydrocarbon receptor (AHR) signaling pathway are associated with the risk of essential hypertension (EH).Design and method:
A genetic association study of the AHR signaling pathway gene polymorphisms with essential hypertension in Russian population. A total of 1908 unrelated Russian subjects including 1140 EH patients and 768 age and sex matched normotensive controls were recruited for this study. Seven common functional polymorphisms such AHR R554K (rs2066853), ARNT 567G > C (rs2228099), AHRR Pro185Ala (rs2292596), CYP1A1 I462 V (rs1048943), CYP1A2 154C > A (rs762551), CYP1B1 V432L (rs1056836), NQO1 P187S (rs1800566) were selected for the study. The polymorphisms were genotyped using TaqMan-based assays.Results:
We found that carriers for variant genotypes (567GC plus CC) of the ARNT gene were at an increased risk of EH (odds ratio = 1.23; 95% confidence interval: 1.02–1.48, P = 0.03). Moreover, a genotype 154AA of the CYP1A2 gene was associated with decreased risk of EH (odds ratio = 0.74; 95% confidence interval: 0.55–0.98, P = 0.04).Conclusions:
To the best of our knowledge, this is the first study reporting associations between AHR signaling pathway genes and the risk of essential hypertension. AHR signaling represents a very promising target for prevention and treatment of hypertension due to its role in heart and vascular physiology, blood pressure regulation and vascular nitric oxide generation. However, AHR is an orphan nuclear receptor with a primary function of mediating xenobiotic metabolism through transcriptional activation of Phase I and Phase II biotransformation enzymes, suggesting a potential role of this pathway in the mechanisms of air pollution-induced hypertension. Our preliminary study findings demonstrate a potential importance of polymorphic genes mediating adaptive and toxic responses to environmental xenobiotics such as halogenated aromatic hydrocarbons in the development of human hypertension. Further investigations are required to confirm the contribution of these genes to essential hypertension risk in independent populations, to assess gene-environment interactions underlying this susceptibility and to designate novel options for disease treatment and prevention. The study was supported by Russian Science Foundation (number 15–15-10010).