The V433M variant of the CYP4F2 is associated with ischemic stroke in male swedes beyond its effect on blood pressure
The V433M variant of the CYP4F2 is associated with ischemic stroke in male swedes beyond its effect on blood pressure
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DOI：
10.1161/hypertensionaha.108.114199
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发表时间：
2008-08-01
期刊：
影响因子：
8.3
通讯作者：
Melander, Olle
中科院分区：
文献类型：
--
作者：
Fava, Cristiano;Montagnana, Martina;Melander, Olle
细胞色素（CYP）4A 11和CYP 4F 2负责肾脏产生20-羟基二十碳四烯酸（一种血管收缩剂和利钠物质）。CYP 4A 11 F434 S和CYP 4F 2 V433 M多态性在体外减少20-羟基二十碳四烯酸的产生。本研究的目的是评估这些多态性对中年瑞典人血压（BP）水平、高血压患病率和心血管事件风险的影响。在马尔莫“饮食与癌症研究”的心血管队列中对多态性进行基因分型。在10年的随访中监测心血管事件（冠状动脉事件，n = 276;缺血性卒中，n = 199）的发生率。对血压水平进行了两次分析：排除或纳入接受抗高血压治疗的受试者。在整个人群中，CYP 4A 11 S434 S纯合子具有较高的收缩压，无论是粗血压还是根据抗高血压药物的数量调整的血压，并且与F434携带者相比，高血压患病率较高。与V433 V纯合子相比，男性（而非女性）CYP 4F 2 M433携带者具有显著更高的粗血压和调整后的收缩压和舒张压，并有更高的高血压患病率趋势（P = 0.06）。校正主要心血管风险因素后，即使将基线BP水平和高血压患病率纳入考克斯比例风险模型，男性CYP 4F 2 M433携带者发生缺血性卒中的风险比仍显著高于V433 V纯合子（风险比：1.69; 95% CI：1.10 - 2.60）。一种常见的CYP 4F 2 V433 M多态性可能仅部分通过其对血压的升高作用而增加男性受试者发生缺血性卒中的风险。需要更多的研究来证实这些数据。
Cytochrome (CYP) 4A11 and CYP4F2 are responsible for renal production of 20-hydroxyeicosatetraenoic acid, a vasoconstrictor and natriuretic substance. The CYP4A11 F434S and CYP4F2 V433M polymorphisms reduce 20-hydroxyeicosatetraenoic acid production in vitro. The aim of the present study was to evaluate the effect of these polymorphisms on blood pressure ( BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. The polymorphisms were genotyped in the cardiovascular cohort of the Malmo "Diet and Cancer Study. The incidence of cardiovascular events ( coronary events, n = 276; ischemic stroke, n = 199) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment. In the whole population, CYP4A11 S434S homozygotes had higher systolic BP, both crude and adjusted for the number of antihypertensive drugs, and higher prevalence of hypertension with respect to F434 carriers. Male, but not female, CYP4F2 M433 carriers had significantly higher crude and adjusted systolic and diastolic BPs and a trend toward higher hypertension prevalence ( P = 0.06) with respect to V433V homozygotes. After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male CYP4F2 M433 carriers was significantly higher with respect to V433V homozygotes ( hazard ratio: 1.69; 95% CI: 1.10 to 2.60) even when baseline BP levels and hypertension prevalence were included in the Cox proportional hazard model. A common CYP4F2 V433M polymorphism might increase the risk of incident ischemic stroke in male subjects only partially through its elevating effect on BP. Additional studies are needed to confirm these data.