Deutsches Herzzentrum München, 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Thromb Haemost. 2010 Jun;103(6):1170-80. doi: 10.1160/TH09-10-0702. Epub 2010 Mar 29.
We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p <or= 0.34). The adjusted odds ratio (OR) for 4G allele carriers was 1.02 (95% confidence interval [CI] 0.87-1.19) compared to the 5G5G genotype. None of 13 common (frequency >1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99-1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00-1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis.
我们评估了丝氨酸蛋白酶抑制剂 1（PAI1）基因座的常见变异与心肌梗死（MI）之间的关联。在一个包含 3657 例 MI 患者和 1211 例对照的德国样本中，分析了包括 4G/5G 缺失/插入多态性和七个单核苷酸多态性的单体型标签多态性。在对 32 项研究（13267 例病例/14716 例对照）提取的数据进行的荟萃分析中，检查了 4G/5G 多态性与 MI 的关系。此外，在一项包括 43 项研究（17278 例病例/18039 例对照）的综合分析中，评估了 4G/5G 多态性与包含 MI、冠状动脉疾病、冠心病或急性冠状动脉综合征的冠状动脉疾病之间的关系。在本样本中，没有一个标签多态性与 MI 相关（p<0.05）。与 5G5G 基因型相比，4G 等位基因携带者的调整比值比（OR）为 1.02（95%置信区间[CI]0.87-1.19）。没有一个常见（频率>1.0%）的 8 标记单体型与 MI 风险相关。在专门针对与 MI 关联的荟萃分析中，4G 等位基因携带者没有发现风险增加（OR 1.07，95%CI 0.99-1.16；p=0.11）。对冠状动脉疾病的更一般综合分析显示，4G 等位基因携带者的风险略有增加（OR 1.08，95%CI 1.00-1.16；p=0.044）。总之，在德国样本中，包括 4G/5G 多态性在内的单体型标签多态性以及丝氨酸蛋白酶抑制剂 1 基因区域的常见单体型与 MI 无关，并且在荟萃分析中也没有获得 4G/5G 多态性与 MI 和冠状动脉粥样硬化之间关系的令人信服的证据。
