The cytochrome P4501A1 T6325C polymorphism is associated with the risk of hypertension

Abstract

Cytochrome P4501A1 (CYP1A1) catalyses the hydroxylation of estradiol and arachidonic acid (AA) producing vasoactive substances, such as catecholestrogens and eicosanoids. Estrogens and eicosanoids are considered to be involved in the pathophysiology of hypertension. However the role of Cytochrome P4501A1 activity in the pathophysiology of hypertension is unclear. CYP1A1 has been known to express genetic variance. Some of its polymorphisms are associated with changes in Cytochrome P4501A1 activity. The C allele of T6325C and the G allele of A4889G polymorphisms have been associated with elevated cytochrome P4501A1 activity. We hypothesized that CYP1A1 polymorphisms would be associated with the risk of hypertension.The hypothesis was tested through a case control study in 208 control and 75 hypertensive male and female subjects. Diabetes and thyroid disease were exclusion factors. We determined the genotype for three CYP1A1 polymorphisms (T6325C, A4889G, and C4887A), using PCR-RFLP, in our population. We observed that the C allele of the CYP1A1 T6325C polymorphism was associated with hypertension (p=0.008, chi-square test). The odds ratio was 2.3 with a 95% confidence interval of 1.3 to 4.1. No association was found between the two other CYP1A1 gene polymorphisms and hypertension. These results implicate the C allele of the CYP1A1 T6325C polymorphism as a risk factor for the development of hypertension and suggest that the activity of cytochrome P4501A1 may play a role in the pathophysiology of this disease.