The influence of CYP2R1 polymorphisms and gene-obesity interaction with hypertension risk in a Chinese rural population

Background and aims: Several studies have reported that variants in CYP2R1 have been linked with an increased risk of hypertension. However, the interaction between CYP2R1 variants and environmental factors on the susceptibility of hypertension remained unclear. Therefore, this study evaluated the influence of CYP2R1 polymorphisms on hypertension susceptibility, and explored the interaction effect of CYP2R1 variations and obesity on the disease.

Methods and results: We included 766 incident hypertension cases matched with non-hypertension controls in a 1:1 ratio by sex, age (within 3 years). Two loci in CYP2R1 gene (rs10766197 and rs12794714) were genotyped by TaqMan probe assays. The concentration of 25-hydroxyvitamin-D was determined by human enzyme-linked immunosorbent assay (ELISA) kits. The associations of CYP2R1 polymorphisms and risks of vitamin D deficiency (VDD) were analyzed by logistic regression. Multifactor dimensionality reduction (MDR) was used to analyze the gene-environment interaction. Multiple logistic regression was used to examine the effect of CYP2R1 gene variations, and the interaction between CYP2R1 variation and obesity on hypertension susceptibility. The results showed that rs10766197 (GG vs. AA) and rs12794714 (GG vs. AA) polymorphisms were both associated with an increased risk of VDD (OR = 1.49, 95% confidence interval (CI) = 1.08-2.05 and OR = 1.63, 95% CI = 1.19-2.25, respectively), after adjustment for potential risk factors. We also found that rs12794714 polymorphism was significantly associated with elevated risk of hypertension under the dominant model (OR = 1.26, 95% CI = 1.01-1.56). In addition, the interactions between rs12794714 with both general obesity (OR = 3.93, 95% CI = 2.72-5.68) and central obesity (OR = 3.22, 95% CI = 2.29-4.52) have significant effects on hypertension susceptibility.

Conclusions: The study provided further evidence that CYP2R1 variation was associated with a higher risk of hypertension in Chinese rural population. The interaction between CYP2R1 rs12794714 and obesity may increase the risk of hypertension.