Hubacek J A, Staněk V, Gebauerová M, Poledne R, Aschermann M, Skalická H, Matoušková J, Kruger A, Pěnička M, Hrabáková H, Veselka J, Hájek P, Lánská V, Adámková V, Pitˇha J
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic,
Mol Biol Rep. 2015 Aug;42(8):1289-93. doi: 10.1007/s11033-015-3870-1. Epub 2015 Mar 26.
Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the traditional risk factors for MI are responsible for approximately 50% of cases of MI cases. Attention therefore has recently focused on genetic variants that are not associated with conventional risk factors. One of them is the marker rs6922269, which has been suggested as a risk factor for development of MI in Western populations. We analyzed the relationship between rs6922269 variant on MTHFD1L gene and (i) risk of the acute coronary syndrome (ACS) in the Czech population and (ii) mortality in 7 years follow up. Rs6922269 (G>A) variant was analyzed (CR 99.3% for patients and 98.0% for controls) by PCR-RFLP in consecutively examined 1614 men and 503 women with ACS (age below 65 years) and in population-based controls--1191 men and 1368 women (aged up to 65 years). ANOVA and Chi square were used for statistical analysis. The genotype frequencies were almost identical (P=0.87) in the ACS patients and in controls and no differences were observed, if males (P=0.73) and females (P=0.93) were analysed separately. In addition, rs6922269 polymorphism was not associated with the classical risk factors (dyslipidemia, hypertension, obesity, smoking, diabetes) in control population. Cardiovascular mortality was significantly higher in males, carriers of the AA genotype (P<0.001, OR 2.52, 95% CI 1.40-4.55, for AA vs. +G). We conclude, that rs6922269 variant at MTHFD1L gene could be an important prognostic factor for cardiovascular mortality in patients after ACS.
心肌梗死(MI)是工业化国家的主要死因。所有传统的MI风险因素约占MI病例的50%。因此,近来注意力集中在与传统风险因素无关的基因变异上。其中之一是标记rs6922269,它被认为是西方人群发生MI的一个风险因素。我们分析了MTHFD1L基因上的rs6922269变异与(i)捷克人群急性冠脉综合征(ACS)风险以及(ii)7年随访期死亡率之间的关系。通过PCR-RFLP分析了连续检测的1614例男性和503例女性ACS患者(年龄低于65岁)以及基于人群的对照组——1191例男性和1368例女性(年龄最高65岁)中的rs6922269(G>A)变异(患者的CR为99.3%,对照组为98.0%)。采用方差分析和卡方检验进行统计分析。ACS患者和对照组的基因型频率几乎相同(P=0.87),如果分别分析男性(P=0.73)和女性(P=0.93),则未观察到差异。此外,rs6922269多态性与对照组人群中的经典风险因素(血脂异常、高血压、肥胖、吸烟、糖尿病)无关。AA基因型携带者男性的心血管死亡率显著更高(P<0.001,AA与+G相比,OR为2.52,95%CI为1.40 - 4.55)。我们得出结论,MTHFD1L基因上的rs6922269变异可能是ACS患者心血管死亡的一个重要预后因素。