CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population
BACKGROUND Cytochromes P450 (CYP) 2C9 are polymorphic enzymes which catalyze a wide spectrum of drugs. It is also responsible for the metabolism of arachidonic acid into EETs. EETs are known to be a vasoactive substance and play an important role in a hypertensive episode. Whether the genetic polymorphism of CYP2C9 will affect the vasoactive effect and consequently affect hypertension formation is still unknown. We investigated the association of CYP2C9*2, CYP2C9*3 and CYP2C9*6 with hypertension. METHODS Two hundred and thirty-nine hypertension patients and 265 healthy controls participated in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify CYP2C9*2, CYP2C9*3 and CYP2C9*6. RESULTS CYP2C9*2 and CYP2C9*6 were not detected in our study. The allelic frequency of CYP2C9*3 was 0.015 in hypertension patients in our study. In healthy controls, the allelic frequency of CYP2C9*3 was 0.049. Significant difference existed in CYP2C9*3 frequency between hypertension patients and healthy controls (0.015 for hypertension patients vs. 0.049 for healthy controls; chi2 = 9.728, P < 0.005, OR = 0.277, 95% CI: 0.118-0.651). Also, gender-dependent difference was observed. In females, CYP2C9*3 frequency of hypertension patients was significantly lower than that of healthy controls (chi2 = 11.513, P < 0.001, OR = 0.113, 95% CI: 0.026-0.500). CONCLUSION To our knowledge, this is the first report on CYP2C9 frequencies in hypertension patients. Our study implied that CYP2C9*3 had a secondary protective effect in females, which may be useful for studying hypertension pathogenesis and therapeutics.