Polymorphism in the β2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism -: A multilocus, population-based, prospective genetic analysis
Polymorphism in the β2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism -: A multilocus, population-based, prospective genetic analysis
复制标题
DOI：
10.1161/circulationaha.106.615401
复制
发表时间：
2006-05-09
期刊：
影响因子：
37.8
通讯作者：
Ridker, PM
中科院分区：
文献类型：
--
作者：
Zee, RYL;Cook, NR;Ridker, PM
背景——炎症、血栓形成、凝血和脂质代谢途径中的候选基因与静脉血栓栓塞（VTE）有关。方法和结果：使用医师健康研究队列基线时收集的DNA样本，我们对304名随后发生静脉血栓栓塞的个体（144名特发性病例，156名继发性病例）和2070名未报告血管疾病的个体进行了平均13.2年的随访，对56个候选基因的92个多态性进行了基因分型，以前瞻性地确定这些基因多态性是否与静脉血栓栓塞风险有关。特发性静脉血栓栓塞,除了因子V(莱顿)突变(优势比[或],5.13;95%可信区间(CI), 3.24 - 8.14, P < 0.0001;错误发现率(罗斯福),P < 0.0001),一个N291S脂蛋白脂肪酶基因多态性(优势比,3.09;95%置信区间,1.56至6.09;P = 0.001;罗斯福,P = 0.036)和Q27Eβ(2)肾上腺素能受体基因多态性(优势比,1.40;95%置信区间,1.09至1.79;P = 0.006;罗斯福,P = 0.036)被发现明显与风险增加有关。对于继发性静脉血栓栓塞，Q360H载脂蛋白A4基因多态性（OR, 0.34; 95% CI, 0.18 ~ 0.65; P = 0.001； FDR, P = 0.07）和I50V白介素4受体多态性（OR, 0.66; 95% CI, 0.52 ~ 0.84; P = 0.0009； FDR, P = 0.07）在多重比较调整后与风险降低相关，但在统计学上不显著。结论-这些目前的发现是假设产生的，需要在独立调查中复制和确认。
Background - Candidate genes in inflammation, thrombosis, coagulation, and lipid metabolism pathways have been implicated in venous thromboembolism (VTE).Methods and Results - Using DNA samples collected at baseline in the Physicians' Health Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304 individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases) and among 2070 individuals who remained free of reported vascular disease over a mean follow-up of 13.2 years to prospectively determine whether these gene polymorphisms contribute to the risk of VTE. For idiopathic VTE, in addition to the factor V (Leiden) mutation (odds ratio [OR], 5.13; 95% confidence interval [CI], 3.24 to 8.14; P < 0.0001; false discovery rate [FDR], P < 0.0001), an N291S lipoprotein lipase gene polymorphism (OR, 3.09; 95% CI, 1.56 to 6.09; P = 0.001; FDR, P = 0.036) and a Q27E beta(2)-adrenergic receptor gene polymorphism (OR, 1.40; 95% CI, 1.09 to 1.79; P = 0.006; FDR, P = 0.036) were found to be significantly associated with increased risk. For secondary VTE, a Q360H apolipoprotein A4 gene polymorphism (OR, 0.34; 95% CI, 0.18 to 0.65; P = 0.001; FDR, P = 0.07) and an I50V interleukin-4 receptor polymorphism (OR, 0.66; 95% CI, 0.52 to 0.84; P = 0.0009; FDR, P = 0.07) were moderately, but not statistically and significantly, associated with reduced risk after adjustment for multiple comparisons.Conclusions - These present findings are hypothesis generating and require replication and confirmation in an independent investigation.