HSP70-2基因多态性与体质指数、饮酒的交互作用对维吾尔族缺血性心力衰竭患者预后的影响

Interaction of HSP70-2 gene polymorphism with body mass index and alcohol consumption on the prognosis of Uyghur patients with ischemic heart failure

目的:探讨HSP70-2基因多态性与体质指数(BMI)、饮酒对维吾尔族缺血性心力衰竭(IHF)患者预后的影响及其交互作用。方法:选择2014年6月—2017年6月在乌鲁木齐市友谊医院心内科住院的维吾尔族IHF患者205例,匹配年龄、性别、民族,收集同期在该院门诊体检指标无明显异常的健康体检者200名作为健康对照组。采用聚合酶链反应检测HSP70-2基因+1267多态性。采用多因素非条件logistic回归分析IHF患者预后相关的危险因素,并通过叉生分析法计算交互作用的相对超额风险(RERI),分析HSP70-2基因多态性与BMI、饮酒的交互作用对患者预后的影响。结果:随访3年,205例IHF患者中,预后不良56例(27.32%),预后良好149例(72.68%)。与健康对照组和预后良好组比较,预后不良组饮酒比例明显增加,BMI、左心室射血分数明显降低,丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)明显升高(均P<0.05)。与预后良好组比较,预后不良组HSP70-2基因型AA/AG/GG、A/G等位基因分布差异有统计学意义(均P<0.05),且不同纽约心脏病协会(NYHA)心功能分级IHF患者HSP70-2基因型分布不同(χ^(2)=45.42,P<0.01);A/G等位基因分布也不同,随着心功能级别升高,HSP70-2基因A等位基因频率升高、G等位基因频率降低(χ^(2)=19.14,P<0.01)。多因素logistic回归分析结果显示,饮酒、ALT、AST是IHF患者预后不良的危险因素,而BMI、HSP70-2GG基因型(相比AA基因型)为IHF患者预后不良的保护因素(均P<0.05)。叉生分析结果显示,BMI与HSP70-2基因多态性有显著加性交互作用(RERI=1.15,95%CI:0.54~1.76,P<0.01),对于携带HSP70-2 AA/AG基因型的患者,BMI小于26.5 kg/m^(2)会增加预后不良的风险(OR=7.47,95%CI:2.51~22.22,P<0.01);饮酒与HSP70-2基因多态性无显著加性交互作用(RERI=0.56,95%CI:-6.07~7.20,P>0.05)。结论:维吾尔族IHF患者HSP70-2基因多态性与BMI具有交互作用,携带AA/AG基因型、BMI小于26.5 kg/m^(2)会增加IHF患者预后不良的风险。

Objective:To investigate the interaction of HSP70-2 gene polymorphism with body mass index(BMI) and alcohol consumption on the prognosis of Uyghur patients with ischemic heart failure(IHF).Methods:A total of 205 Uyghur patients with IHF admitted in Urumqi Friendship Hospital from June 2014 to June 2017 were enrolled;200 age and sex-matched healthy Uyghur physical examiners in the hospital were enrolled as healthy controls.The HSP70-2 gene +1267 polymorphism was detected by PCR.Multivariate unconditional logistic regression was used to analyze the risk factors associated with prognosis in patients with IHF,and the relative excess risk of interaction(RERI) was calculated by crossover analysis to determine the interaction of HSP70-2 gene polymorphism with BMI and alcohol consumption.Results:Patients were followed up for 3 years,there were 56 cases with poor prognosis(27.32%) and 149 cases with good prognosis(72.68%).Compared with the healthy control group and the good prognosis group,the poor prognosis group had a significantly higher proportion of subjects with alcohol consumption,abnormal alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels as well as lower BMI and left ventricular ejection fraction(all P<0.05).There were significant differences in distributions of HSP70-2 genotype AA/AG/GG and A/G allele between the good prognosis group and the poor prognosis group(both P<0.05).There were significant differences in the distribution of HSP70-2 genotype(χ^(2)=45.42,P<0.01) and A/G allele among IHF patients with different NYHA cardiac function class;the frequency of A allele of HSP70-2 gene increased,and G allele decreased with the increase of cardiac function class(χ^(2)=19.14,P<0.01).Multivariate logistic regression analysis showed that alcohol consumption as well as abnormal ALT and AST were risk factors for poor prognosis in patients with IHF,while BMI and GG type of HSP70-2 gene(compared with AA type) were protective factors(all P<0.05).Crossover analysis showed a significant additive interaction between BMI and HSP70-2 gene polymorphism(RERI=1.15,95%CI:0.54-1.76,P<0.01),and for patients carrying HSP70-2 gene type AA/AG,BMI26.5 kg/m^(2) increased the risk of poor prognosis(OR=7.47,95%CI:2.51-22.22,P<0.01);there was no significant additive interaction between alcohol consumption and HSP70-2 gene polymorphism(RERI=0.56,95%CI:-6.07-7.20,P>0.05).Conclusion:The HSP70-2 gene polymorphism interacts with BMI in Uyghur IHF patients,and BMI26.5 kg/m^(2) increases the risk of poor prognosis in IHF patients carrying the HSP70-2 AA/AG genotype.