炎症相关基因多态性与心脏瓣膜置换术后华法林治疗疗效的相关性研究

Correlation Between Inflammation-related Gene Polymorphisms and Efficacy of Warfarin Therapy after Heart Valve Replacement Surgery

目的探索炎性基因基质金属蛋白酶2(MMP2)的一种G/C多态现象与心脏瓣膜置换术后华法林治疗的关系。方法纳入2010年1月至2015年1月在我院胸心外科行心脏瓣膜置换术后华法林治疗的患者96例作为试验组,另纳入心脏瓣膜置换术后未采用华法林治疗的患者78例作为对照组,采用基因测序的方法确定单核苷酸多态性的等位基因,分析两组患者的基因型与临床特点,探讨心脏瓣膜置换术后华法林治疗与不同的MMP2基因型之间的关系。采用logistic回归分析基因型与心脏瓣膜置换术后危险因素之间的相关性;运用Kaplan-Meier生存曲线对携带MMP2 GC与GG两种基因型患者的生存与疗效情况进行分析。结果 MMP2基因型在术后采用华法林治疗与未采用华法林治疗的基因型分布是不相同的,多因素logistic回归分析显示GC与GG两种基因型是心脏瓣膜置换术后并发症发生的危险因素。术后并发症发生的患者GG基因型的比例要高于未出现并发症患者,治疗疗效及生存分析方面,携带MMP2 GG基因型的患者生存时间要短于携带GC基因型,两组差异有统计学意义,MMP2 GG基因型表达的高低与预后有着一定的相关性。结论 MMP2的G等位基因是心脏瓣膜置换术后并发症发生的危险因素,GG基因型与心脏瓣膜置换治疗及预后有相关性,可作为心脏瓣膜置换术后危险因素。

Objective To clarify the relationship between the G/C polymorphism of inflammatory gene matrix metalloproteinase-2 （MMP2） and warfarin therapy after cardiac valve replacement （CVR）. Methods We finally identified 96 patients who received additional warfarin therapy after CVR as a trial group and 78 patients without the warfarin therapy as a control group. Gene sequencing techniques were adopted to determine single nucleotide polymorphism allele. We analyzed genotype and clinical features of the two groups and explored the relationship between the different MMP2 geno- types and warfarin therapy after CVR. Logistic regression was used to analyze the correlation between genotypes and risk factors after CVR and Kaplan-Meier survival curves were performed to analyze the survival time and efficacy of patients carrying MMP2 GC and GG genotypes. Results The distribution of MMP2 genotype in patients receiving warfarin therapy after surgery was different from that in patients without warfarin therapy. The results of multivariate logistic regression analysis showed that GC and GG genotypes were risk factors of complications of CVR. The proportion of GG genotype was higher in the patients with postoperative complications compared with those without. The survival time of patients carrying genotype MMP2 GG was shorter than those carrying GC genotype （P〈0.05）, which reveals that the level of MMP2 GG genotype was associated with the prognosis. Conclusion G allele of MMP2 is a risk factor of complications following CVR. GG genotype is relevant to CVR and prognosis, which can be regarded as a risk factor post CVR.