β2-肾上腺素能受体和脂蛋白脂肪酶基因多态性作为特发性静脉血栓栓塞症的风险决定因素：一项基于人群的多位点前瞻性基因分析。

Polymorphism in the beta2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism: a multilocus, population-based, prospective genetic analysis.

作者信息

Zee Robert Y L, Cook Nancy R, Cheng Suzanne, Erlich Henry A, Lindpaintner Klaus, Ridker Paul M

机构信息

Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Circulation. 2006 May 9;113(18):2193-200. doi: 10.1161/CIRCULATIONAHA.106.615401. Epub 2006 May 1.

DOI:10.1161/CIRCULATIONAHA.106.615401

PMID:16651467

Abstract

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 beta2-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.

摘要

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症（VTE）有关。

方法与结果

利用医师健康研究队列基线时收集的DNA样本，我们对56个候选基因中的92个多态性进行了基因分型，这些基因分型来自304名随后发生VTE的个体（144例特发性VTE，156例继发性VTE）以及2070名在平均13.2年的随访期内未报告有血管疾病的个体，以前瞻性地确定这些基因多态性是否会增加VTE风险。对于特发性VTE，除了因子V（Leiden）突变（比值比[OR]，5.13；95%置信区间[CI]：3.24至8.14；P<0.0001；错误发现率[FDR]，P<0.0001）外，脂蛋白脂肪酶基因N291S多态性（OR，3.09；95%CI，1.56至6.09；P=0.001；FDR，P=0.036）和β2 - 肾上腺素能受体基因Q27E多态性（OR，1.40；95%CI，1.09至1.79；P=0.006；FDR，P=0.036）与风险增加显著相关。对于继发性VTE，载脂蛋白A4基因Q360H多态性（OR，0.34；95%CI，0.18至0.65；P=0.001；FDR，P=0.07）和白细胞介素 - 4受体I50V多态性（OR，0.66；95%CI，0.52至0.84；P=0.0009；FDR，P=0.07）在经过多重比较校正后与风险降低呈中度相关，但无统计学显著意义。