Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery.
Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery.
复制标题
DOI：
10.1016/j.jtcvs.2009.06.032
复制
发表时间：
2010-02
影响因子：
6
通讯作者：
Shernan, Stanton K.
中科院分区：
文献类型：
--
作者：
Liu, Kuang-Yu;Muehlschlegel, Jochen D.;Perry, Tjoervi E.;Fox, Amanda A.;Collard, Charles D.;Body, Simon C.;Shernan, Stanton K.
大约 10% 接受心脏手术的患者会遭受围手术期心肌损伤 (PMI)。最近的一项全基因组关联研究发现，非手术人群的心肌梗塞与 9p21 号染色体上的常见遗传变异之间存在关联。我们假设这些变异也与孤立性原发性冠状动脉旁路移植术 (CABG) 手术后的 PMI 相关。在对美国 2 个中心的 846 名原发性 CABG 手术患者进行的一项前瞻性观察研究中，我们对 61 个连锁不平衡标记单核苷酸多态性 (SNP) 进行了基因分型，涵盖 9p21 区域的 436 kbp。使用多变量逻辑模型来调整先前确定的 PMI 临床协变量。 PMI 定义为术后第 1 天心肌肌钙蛋白 I (cTnI) 位于队列前 10 个百分位 (> 9.13 μg/L)。 SNP 的多重测试已通过家族 (FW) 错误进行纠正。既往心肌梗死和较长的体外循环时间是 PMI 的重要独立预测因素。三个 SNP（rs10116277、rs6475606 和 rs2383207）的风险等位基因每增加一个副本，术后 cTnI 水平就会逐渐增加。调整后的加性比值比范围在 1.64 和 1.79 之间（渐近 P 值在 3.7 × 10-3 - 6×10-4 之间），即使在考虑了包括冠心病严重程度在内的临床协变量和多重比较后，仍与 PMI 显着相关。我们现在已经证明，先前已知与非手术人群心肌梗塞相关的 9p21 常见遗传变异也与 CABG 后的 PMI 相关。需要进一步研究以阐明功能机制。我们确定了初次 CABG 手术患者 9p21 区域的常见遗传变异与术后 cTnI 水平之间的关联，每增加一个风险等位基因拷贝，cTnI 水平就会逐渐增加。即使考虑了包括冠心病严重程度在内的临床协变量，这种关联仍然非常显着。
Approximately 10% of patients undergoing cardiac surgery suffer perioperative myocardial injury (PMI). A recent genome-wide association study identified an association between myocardial infarction in non-surgical populations and common genetic variants on chromosome 9p21. We hypothesized that these variants are also associated with PMI after isolated primary coronary artery bypass graft (CABG) surgery. In a prospective observational study of 846 Caucasian primary CABG surgery patients at 2 US centers, we genotyped 61 linkage disequilibrium tagging single nucleotide polymorphisms (SNPs), encompassing 436 kbp of the 9p21 region. A multivariable logistic model was used to adjust for previously identified clinical covariates of PMI. PMI was defined as a postoperative day 1 cardiac Troponin I (cTnI) in the top 10th percentile (> 9.13 μg/L) of the cohort. Multiple testing of SNPs was corrected for with family-wise (FW) errors. Prior myocardial infarction and longer cardiopulmonary bypass time were significant independent predictors of PMI. Levels of postoperative cTnI were incrementally increased for each additional copy of the risk alleles of three SNPs: rs10116277, rs6475606 and rs2383207. Adjusted additive odds ratios ranged between 1.64 and 1.79 (asymptotic P value between 3.7 × 10-3 - 6×10-4) and remained significantly associated with PMI even after accounting for clinical covariates including severity of coronary disease, and multiple comparisons. We have now demonstrated that common genetic variants in 9p21 previously known to be associated with myocardial infarction in non-surgical populations, are also associated with PMI after CABG. Further investigation is warranted to elucidate functional mechanisms. We identified an association between common genetic variants in the 9p21 region in primary CABG surgery patients and levels of postoperative cTnI, which were incrementally increased for each additional copy of the risk alleles. The association remained highly significant even after accounting for clinical covariates including severity of coronary disease.
登录
查看更多内容
DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
30.8
作者：
Helgadottir, Anna;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
168.9
作者：
Yusuf, S;Hawken, S;Liu, LS
通讯作者：
Liu, LS
影响因子：
1.9
作者：
Abdullah, K. G.;Li, L.;Wang, Q. K.
通讯作者：
Wang, Q. K.
影响因子：
37.8
作者：
Podgoreanu, MV;White, WD;Schwinn, DA
通讯作者：
Schwinn, DA