Collard Charles D, Shernan Stanton K, Fox Amanda A, Bernig Toralf, Chanock Stephen J, Vaughn William K, Takahashi Kazue, Ezekowitz Alan B, Jarolim Petr, Body Simon C
Baylor College of Medicine, Texas Heart Institute, St Luke's Episcopal Hospital, 6720 Bertner Avenue, Houston, TX 77030, USA.
Circulation. 2007 Sep 11;116(11 Suppl):I106-12. doi: 10.1161/CIRCULATIONAHA.106.679530.
Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery.
Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705).
The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery.
甘露糖结合凝集素（MBL）是天然免疫的重要组成部分及凝集素补体途径的激活剂。MBL2基因内有7种5'“分泌型”单倍型，其编码的血清MBL水平及补体激活存在改变。然而，最近有证据表明3' MBL2单倍型也可能影响MBL功能及循环水平。由于MBL和凝集素补体途径与心血管损伤有关，我们研究了MBL2单倍型是否与冠状动脉搭桥手术患者术后心肌梗死（PMI）风险增加独立相关。
在一项前瞻性、纵向多机构研究中，对978例于2001年8月至2005年5月期间仅接受初次冠状动脉搭桥手术并行体外循环的患者，进行了MBL2基因内18个多态性位点的基因分型。通过置换检验对多重比较进行校正后，进行多变量逐步逻辑回归分析，包括得分检验，控制患者人口统计学特征、术前危险因素、用药情况及术中变量，以确定MBL2分泌型单倍型是否为初次冠状动脉搭桥手术白人患者PMI的独立预测因素。单独的5'或3' MBL2单倍型均与PMI发生率增加无关。然而，表达MBL2 5' LYQA分泌型单倍型（CGTCGG）和3'单倍型（CGGGT）的白人（n = 843）中PMI发生率显著高于未表达该单倍型的白人（38%对10%；P < 0.007）。此外，在调整其他协变量后，MBL2 LYQA分泌型单倍型组合是初次冠状动脉搭桥手术后白人患者PMI的独立预测因素（P < 0.02；调整后OR：3.97；95% CI：1.30至12.07）。白人中MBL2 LYQA分泌型单倍型组合也是术后CKMB水平超过60 ng/mL的独立预测因素（P < 0.02；调整后OR：4.48；95% CI：1.95至16.80）。纳入MBL2 LYQA分泌型单倍型组合可改善仅基于传统危险因素的PMI预测模型（C统计量0.715对0.705）。
MBL2 LYQA分泌型单倍型组合是PMI的一种新型独立预测因素，可能有助于初次冠状动脉搭桥手术白人患者的术前风险分层。
