Yu Bang-ning, Luo Chen-Hui, Wang Dan, Wang An, Li Zhi, Zhang Wei, Mo Wei, Zhou Hong-Hao
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, China.
Clin Chim Acta. 2004 Oct;348(1-2):57-61. doi: 10.1016/j.cccn.2004.04.028.
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 CYP2C92, CYP2C93 and CYP2C9*6 with hypertension.
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 CYP2C92, CYP2C93 and CYP2C9*6.
CYP2C92 and CYP2C96 were not detected in our study. The allelic frequency of CYP2C93 was 0.015 in hypertension patients in our study. In healthy controls, the allelic frequency of CYP2C93 was 0.049. Significant difference existed in CYP2C93 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, CYP2C93 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).
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.
细胞色素P450(CYP)2C9是一种多态性酶,可催化多种药物。它还负责将花生四烯酸代谢为环氧二十碳三烯酸(EETs)。已知EETs是一种血管活性物质,在高血压发作中起重要作用。CYP2C9的基因多态性是否会影响血管活性作用,进而影响高血压的形成尚不清楚。我们研究了CYP2C92、CYP2C93和CYP2C9*6与高血压的关联。
239例高血压患者和265例健康对照参与了我们的研究。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法鉴定CYP2C92、CYP2C93和CYP2C9*6。
本研究未检测到CYP2C92和CYP2C96。本研究中高血压患者CYP2C93等位基因频率为0.015。在健康对照中,CYP2C93等位基因频率为0.049。高血压患者和健康对照之间CYP2C93频率存在显著差异(高血压患者为0.015,健康对照为0.049;χ2 = 9.728,P < 0.005,OR = 0.277,95% CI:0.118 - 0.651)。此外,还观察到性别依赖性差异。在女性中,高血压患者的CYP2C93频率显著低于健康对照(χ2 = 11.513,P < 0.