Dallongeville Jean, Cottel Dominique, Montaye Michèle, Codron Valérie, Amouyel Philippe, Helbecque Nicole
Service d'Epidémiologie et de Santé Publique-INSERM U-508 & Departement d'atherosclerose, lnstitut Pasteur de Lille, France.
Int J Cardiol. 2006 Jan 13;106(2):152-6. doi: 10.1016/j.ijcard.2004.10.065.
The goal of the present study was to assess the impact of 4 single nucleotide polymorphisms (SNPs) of APOA5/A4/C3 gene cluster on lipid levels and coronary heart disease (CHD) risk in French men.
A total of 442 men with CHD were recruited from the university hospital and compared to 475 men free of CHD from the population of the same geographical area. The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined.
The APOA5 S19W polymorphism was associated with plasma triglyceride levels. In multivariate logistic regression analyses the odds ratio (OR [95% Cl]) of hypertriglyceridemia (3rd vs. 1st tertile of triglyceride distribution) was 3.60 [1.38-9.42] in control subjects bearing at least one APOA5 19W variant. Haplotype analyses revealed a significant association between the 2111 haplotype and high triglyceride levels (+1.94 +/- 0.63 vs. 0.74 +/- 0.36 mmol/l for the 1111 haplotype p < 0.002). There was, in contrast, no significant difference in SNP distribution between CHD patients and controls. The age-adjusted OR of CHD were 1.46 [0.96-2.23], 0.79 [0.60-1.05], 0.91 [0.69-1.21] and 0.91 [0.69-l.22] in carriers of the APOA5 19W, APOA5 -12,238C, APOA4 347S and APOC3 -482T variants, respectively. There was also no significant difference in APOA5/A4/C3 haplotype distribution in patients and controls.
The APOA5 19W variant is associated with increased plasma triglycerides. However, there is no evidence that APOA5 S19W, -12,238T > C, APOA4 T347S and APCC3 -482C > T SNPs are major risk factors of CHD in French men.
本研究旨在评估载脂蛋白A5/A4/C3基因簇的4个单核苷酸多态性（SNP）对法国男性血脂水平和冠心病（CHD）风险的影响。
从大学医院招募了442例冠心病男性患者，并与来自同一地理区域人群的475例无冠心病男性进行比较。检测了载脂蛋白A5 S19W、载脂蛋白A5 -12,238T>C、载脂蛋白A4 T347S和载脂蛋白C3 -482C>T这几个SNP。
载脂蛋白A5 S19W多态性与血浆甘油三酯水平相关。在多因素逻辑回归分析中，至少携带一个载脂蛋白A5 19W变异的对照受试者中，高甘油三酯血症（甘油三酯分布的第3三分位数与第1三分位数相比）的优势比（OR [95%CI]）为3.60 [1.38 - 9.42]。单倍型分析显示，2-1-1-1单倍型与高甘油三酯水平显著相关（2-1-1-1单倍型为+1.94±0.63 mmol/l，1-1-1-1单倍型为0.74±0.36 mmol/l，p<0.002）。相比之下，冠心病患者和对照之间的SNP分布没有显著差异。载脂蛋白A5 19W、载脂蛋白A5 -12,238C、载脂蛋白A4 347S和载脂蛋白C3 -48,2T变异携带者中，经年龄调整的冠心病OR分别为1.46 [0.96 - 2.23]、0.79 [0.60 - 1.05]、0.91 [0.69 - 1.21]和0.91 [0.69 - 1.22]。患者和对照之间的载脂蛋白A5/A4/C3单倍型分布也没有显著差异。
载脂蛋白A5 19W变异与血浆甘油三酯升高相关。然而，没有证据表明载脂蛋白A5 S19W、-12,238T>C、载脂蛋白A4 T347S和载脂蛋白C3 -482C>T这几个SNP是法国男性冠心病的主要危险因素。
