NOS1AP基因单核苷酸多态性位点rs10494366与埋藏式心脏复律除颤器二级预防患者室性心律失常事件的相关性评估

Correlation between rs10494366 of single nucleotide polymorphism in NOS1AP gene and ventricular arrhythmias events in patients with implantable cardioverter defibrillator for secondary prevention

目的借助埋藏式心脏复律除颤器(ICD)记录的事件探讨一氧化氮合酶1衔接蛋白(NOS1AP)基因rs10494366位点TT基因型在ICD二级预防患者室性心律失常事件中的预测价值。方法入选2013年9月至2017年6月于郑州大学人民医院心律失常病区行ICD植入的二级预防患者122例为病例组,入选同期于体检中心体检的348例健康体检人群为对照组。在ICD二级预防患者及健康对照人群中对NOS1AP基因rs10494366位点行病例-对照研究,分析该位点TT基因型是否和ICD二级预防患者相关。对入选对象进行长期随访,在ICD植入后第3月、第12月及第3年进行程控检查,对记录的快速室性心律失常事件及恰当治疗事件与三种基因型(GG、GT、TT)进行相关性分析,同时评估rs10494366位点三种基因型对死亡率的影响。结果rs10494366位点TT基因型和QT间期的延长显示了正相关性(β=9.443,P=0.020)。病例-对照研究显示rs10494366位点TT基因型和ICD恰当治疗患者相关(等位基因模式下P=0.014)。经过31.70±9.15个月的随访,发现rs10494366位点三种基因型患者的ICD放电次数具有差异(Z=7.628,P=0.022),TT基因型增加了ICD放电频率和次数。进一步通过Kaplan-Meier曲线显示TT基因型患者较其他两种基因型生存预后较差(P=0.005);Cox回归分析发现,rs10494366 TT基因型是心源性猝死的高风险因素,与GG基因型相比死亡风险增加2.944倍(P=0.014)。结论NOS1AP基因中rs10494366位点TT基因型增加了ICD二级预防患者放电治疗事件,可做为此类患者的风险预测因子,临床检测该位点的基因型具有一定参考价值。

Objective To investigate the predictive value of genotype TT in rs10494366 site in NOS1AP gene to events of ventricular arrhythmias(VA)in patients with implantable cardioverter defibrillator(ICD)for secondary prevention.Methods The patients with ICD were chosen into case group(n=122)and heathy controls were chosen into control group(348)from the Second Area of Arrhythmias,People’s Hospital,Zhengzhou University from Sept.2013 to June 2017.The correlation between genotype TT of rs10494366 site in NOS1AP gene and ICD was analyzed by using case-control study.All objects were followed up for a long time,and they were given a programmed examination on the 3rd month,12th month and 3rd year after ICD implantation.The correlation among VA events,appropriate treatment and 3 genotypes(genotypes GG,GT and TT)was analyzed.Meanwhile the influences of genotypes GG,GT and TT in rs10494366 site on mortality were reviewed.Results The genotype TT in rs10494366 site was positively correlated to prolonged QT interval(β=9.443,P=0.020).The results off case-control study showed that genotype TT in rs10494366 site was correlated to patients with ICD and appropriate treatment(P=0.014 in allele mode).After followed up for(31.70±9.15)months,there was difference in ICD discharge times(Z=7.628,P=0.022)in patients with 3 genotypes in rs10494366 site,and ICD discharge frequency and times were increased in patients with genotype TT.The results of Kaplan-Meier curve analysis showed that the survival prognosis was poorer in patients with genotype TT than that in patients with other 2 genotypes(P=0.005).The results of Cox regression analysis showed that genotype TT in rs10494366 site was a high-risk factor of sudden cardiac death(SCD),and mortality risk of genotype TT increased by 2.944 compared with genotype GG(P=0.014).Conclusion The genotype TT in rs10494366 site in NOS1AP gene increases discharge treatment events in patients with ICD for secondary prevention,which can be taken as a factor for risk prediction.Therefore,detecting the genotype in this site has some reference value in clinical practice.