The present study was designed to examine a relationship between common polymorphism C3435T of the ABCB1 gene and risk of essential hypertension (EH) and to test the hypothesis whether associations of the ABCB1 genotypes with disease risk is modified by smoking status.Design and method:
A genetic association study of polymorphism C3435T of the ABCB1 gene with essential hypertension in Russian population. A total of 2 220 unrelated Russian individuals from Central Russia were recruited for this study. The study participants included 1 370 EH patients and 850 age and sex matched healthy subjects. Genotyping of polymorphism C3435T (rs1045642) of the ABCB1 gene was done through a TaqMan-based assay.Results:
We found that the carriers of variant genotypes (i.e. 3435CT plus TT) of the ABCB1 gene possessed an increased risk of EH (odds ratio = 1.23; 95% confidence interval: 1.02–1.48, P = 0.03). The gene-smoking interaction analysis has revealed that a carriage of the 3435CT/TT genotypes is associated with increased EH risk only in cigarette smokers (OR = 1.42 95%CI 1.04–1.94, P = 0.03), whereas non-smoker carriers of these genotypes were not at disease risk. This association remained a statistically significant after adjustment for age, sex and body mass index by a multiple logistic regression analyses (P = 0.04).Conclusions:
This is the first study reporting that the association of ABCB1 C3435T polymorphism with hypertension is modified by smoking status. ABCB1 is a membrane-associated P-glycoprotein regulating an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. The 3435T variant is known to cause a decreased activity/expression of P-glycoprotein. It was reported that the ABCB1 expression is downregulated in peripheral blood mononuclear cells of spontaneously hypertensive rats. Our study finding suggests that since P-glycoprotein functions as a transporter of xenobiotic compounds in the blood-brain barrier, a decreased ABCB1 activity/expression in smokers with the variant genotypes may cause high blood pressure possibly through an enhanced sympathetic stimulation due to the accumulation of tobacco-related toxicants in the brain. The study was supported by Russian Science Foundation (number 15–15–10010).