基质金属蛋白酶2基因多态性与缺血性收缩性心衰预后相关

Polymorphisms of MMP-2 Gene are Associated with the Prognosis of Systolic Heart Failure

目的基质金属蛋白酶家族(Matrix metalloproteinases,MMPs)是一组蛋白溶解酶系,在心肌细胞外基质降解过程中发挥重要作用。MMP-2作为家族中的重要成员,在心力衰竭心肌重构过程中起关键作用。我们推测MMP-2基因多态性可能会影响收缩性心衰的预后。方法对387位缺血性收缩性心衰患者进行随访,用限制性片段长度多态性的方法(restriction fragment length polymor- phism,RFLP)分析MMP-2基因的三个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点rs243864,rs243866,rs17859821。结果随访到335位患者,随访率86.6%。在随访期间(0～47个月,中位随访时间24个月),有72例(21.5%)患者死亡,56例(16.7%)患者因心衰再次入院,3例(0.9%)患者再次心肌梗塞,24例(7.2%)再次血运重建。1年、2年、3年的生存率分别是86%、79%、73%。MMP-2 rs17859821 A等位基因携带者全因死亡率、心源性死亡率、心衰死亡率和主要心脏不良事件率(major adverse cardiac event,MACE)均高于GG基因型者(OR=0.513,0.416,0.472,0.671;P=0.010,0.002,0.021,0.022)。使用Cox回归分析校正年龄、束支传导阻滞、LVEF和NYHA分级后,A等位基因携带者心源性死亡率和心衰死亡率仍显著或临界显著低于GG基因型者(OR= 0.475,0.518;P=0.010,0.050)。结论研究结果提示携带MMP-2 rs17859821 A等位基因的缺血性收缩性心衰患者预后较好。

Objective Matrix metalloproteinases （MMPs） are a family of proteolytic enzymes responsible for myocardial extracellular protein degradation. MMP-2 is an important member of MMPs. MMP- 2 has been demonstrated to play a pivotal role in myocardial remodeling process that occurs in congestive heart failure （HF）. We hypothesized MMP-2 genetic variations could influence the prognosis of systolic HF. Methods To test our hypothesis, we performed a follow-up study of 387 patients with systolic HF caused by myocardial infarction. Three single nueleotide polymorphisms （SNPs） of MMP-2 （rs243864, rs243866, rs17859821 ） were analyzed by restriction fragment length polymorphism （RFLP） methods. Results Three hundreds and thirty five patients （86. 6% ） were followed up. At follow up （0-47month, median 24 months）, 72 patients （21.5%） died, 56 patients （ 16.7% ） were readmitted because of HF, 3 patients （0.9%） bad recurrent myocardial infarction, 24 patients （7. 2% ） had repeat revaseularization. One, two, and three year survival rates were 86% , 79% and 73%. All cause death rate, cardiac death rate, HF death rate and MACE rate were lower in MMP-2 rs17859821 A allele carriers than did GG genotype carriers （ OR = 0. 513,0. 416,0. 472, 0. 671 ;P =0. 010,0.002,0.021, 0. 022）. After adjustment for age, bundle branch block, LVEF and NYHA grade by using cox regression analysis, cardiac death rate and HF death rate were still lower in MMP-2 A allele carriers than did GG genotype carriers（ OR = 0. 475 and 0. 518 ;P = 0. 010,0. 050）. Conclusion The findings of the present study suggest that MMP-2 rs17859821 A allele is associated with better prognosis of systolic heart failure in the northern Han Chinese population.