Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.
Prostaglandins Other Lipid Mediat. 2012 May;98(1-2):31-6. doi: 10.1016/j.prostaglandins.2012.03.001. Epub 2012 Mar 30.
The genetic basis of Metabolic syndrome (MetS) is largely unknown but a link with salt sensitivity is recognized. The cytochrome P450 isoform 4F2 (CYP4F2) is involved in renal production of 20-hydroxyeicosatethraenoic acid (20-HETE), a natriuretic substance associated with salt sensitivity. The same enzyme is implicated in ω-hydroxylation of very long and medium chain fatty acids in the liver suggesting its possible influence on gluco-metabolic components of MetS. The aim of the present study was to evaluate the effect of CYP4F2 V433M, a functional polymorphism previously associated with hypertension via renal salt reabsorption, on the individual components of MetS and MetS itself.
The polymorphism was genotyped in the cardiovascular cohort of the Malmö Diet and Cancer (MDC-CVA) study and successively in the Malmö Preventive Project (MPP) cohort. Different definitions of the MetS were applied.
In the MDC-CVA, male, but not female, CYP4F2 M433 carriers had significantly higher levels of waist, triglycerides, BP and a composite sum of MetS phenotypes (MetS score) beside lower HDL-cholesterol respect to V-homozygotes. MetS, as defined in the ATPIII and the AHA/NHLBI definitions, was more prevalent in M-carriers with respect to V-homozygotes. In the MPP cohort, significant association was detectable only for triglycerides at baseline and for Diastolic BP at reinvestigation in male M-carriers.
The initial positive association of the CYP4F2 V433M polymorphism with components of MetS and MetS itself, found in MDC-CVA, was partially denied in another large cohort. The first association either could be due to a false positive result or alternatively, different genetic background or population stratification could have hidden the effect of the polymorphism in the replication cohort.
代谢综合征（MetS）的遗传基础在很大程度上是未知的，但人们认识到它与盐敏感性有关。细胞色素 P450 同工酶 4F2（CYP4F2）参与肾脏产生 20-羟二十碳四烯酸（20-HETE），这是一种与盐敏感性相关的利钠物质。同一酶参与肝脏中极长链和中链脂肪酸的ω-羟化，表明其可能对 MetS 的糖代谢成分有影响。本研究旨在评估 CYP4F2 V433M（先前通过肾脏盐重吸收与高血压相关的功能性多态性）对 MetS 个体成分和 MetS 本身的影响。
该多态性在马尔默饮食和癌症（MDC-CVA）研究的心血管队列中进行了基因分型，随后在马尔默预防项目（MPP）队列中进行了基因分型。应用了不同的 MetS 定义。
在 MDC-CVA 中，男性而非女性 CYP4F2 M433 携带者的腰围、甘油三酯、血压和 MetS 表型的综合总和（MetS 评分）明显高于 V-纯合子，而高密度脂蛋白胆固醇则较低。根据 ATPIII 和 AHA/NHLBI 定义，M 携带者的 MetS 更为普遍。在 MPP 队列中，仅在男性 M 携带者的基线时发现甘油三酯和再检查时的舒张压存在显著相关性。
在 MDC-CVA 中，CYP4F2 V433M 多态性与 MetS 成分和 MetS 本身的最初阳性关联在另一个大型队列中部分被否定。第一个关联可能是由于假阳性结果，或者由于遗传背景或人群分层的不同，导致该多态性在复制队列中的作用被掩盖。
