Hua Yihong, Song Li, Wu Naqiong, Xie Gaoqiang, Lu Xiangfeng, Fan Xiaohan, Meng Xianmin, Gu Dongfeng, Yang Yuejin
Department of Cardiology, Fu Wai Hospital, Beijing, People's Republic of China.
Clin Chim Acta. 2009 Jun 27;404(2):119-23. doi: 10.1016/j.cca.2009.03.030. Epub 2009 Mar 28.
MMP-2 is a proteolytic enzyme involved in myocardial remodeling that occurs in congestive heart failure (HF). We hypothesized MMP-2 genetic variations could influence the prognosis of systolic HF.
To test our hypothesis, we performed a follow-up study of 605 patients with systolic HF. Three single nucleotide polymorphisms (SNPs) of MMP-2 (rs243864, rs243866, rs17859821) were analyzed by restriction fragment length polymorphism (RFLP) methods.
Totally 526 patients (86.9%) were followed up. At follow up (median 24 months), 116 patients (22.1%) died, 102 patients (19.4%) were readmitted because of HF. One, two, three and four year survival rate was 86.9%, 81%, 77.9% and 77.9%. MMP-2 rs17859821 A allele carriers had lower all cause death rate, cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.655, 0.580, 0.705; P = 0.030, 0.008, 0.011). After adjustment for age, bundle branch block, LVEF and NYHA grade by using cox regression analysis, MMP-2 A allele carriers had lower cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.643 and 0.746; P < 0.05). However, the genotypes had no association with plasma levels of proMMP-2. Haplotype analysis had confirmed the above results. MMP-2 rs243866, rs243864 had no association with systolic HF prognosis.
The findings of the present study suggest that MMP-2 rs17859821 A allele was associated with better prognosis of systolic HF in the northern Han Chinese population.
基质金属蛋白酶-2（MMP-2）是一种参与充血性心力衰竭（HF）时心肌重塑的蛋白水解酶。我们假设MMP-2基因变异可能影响收缩性HF的预后。
为验证我们的假设，我们对605例收缩性HF患者进行了一项随访研究。采用限制性片段长度多态性（RFLP）方法分析了MMP-2的三个单核苷酸多态性（SNP）（rs243864、rs243866、rs17859821）。
共526例患者（86.9%）得到随访。随访时（中位时间24个月），116例患者（22.1%）死亡，102例患者（19.4%）因HF再次入院。1年、2年、3年和4年生存率分别为86.9%、81%、77.9%和77.9%。MMP-2 rs17859821 A等位基因携带者的全因死亡率、心源性死亡率和主要不良心血管事件（MACE）发生率均低于GG基因型携带者（OR = 0.655、0.580、0.705；P = 0.030、0.008、0.011）。通过Cox回归分析对年龄、束支传导阻滞、左心室射血分数（LVEF）和纽约心脏协会（NYHA）心功能分级进行校正后，MMP-2 A等位基因携带者的心源性死亡率和MACE发生率低于GG基因型携带者（OR = 0.643和0.746；P < 0.05）。然而，这些基因型与前MMP-2的血浆水平无关。单倍型分析证实了上述结果。MMP-2 rs243866、rs243864与收缩性HF预后无关。
本研究结果表明，在北方汉族人群中，MMP-2 rs17859821 A等位基因与收缩性HF的较好预后相关。
