肿瘤坏死因子受体2基因多态性与冠心病分型的相关性分析

目的研究肿瘤坏死因子受体2基因6号外显子rs1061622(+676)位点的基因型及血浆可溶性肿瘤坏死因子受体2与冠心病临床分型及其危险因素的关系,分析两者与冠心病分型的相关性。方法选取经冠状动脉造影证实为冠心病的患者250例,其中稳定型心绞痛54例、不稳定型心绞痛110例、急性心肌梗死86例;同时选取我院正常体检者98例作为对照组。记录所有研究对象的病史、体格检查、辅助检查、冠状动脉造影结果等临床资料。采用聚合酶链反应-连接酶检测反应的方法检测各组肿瘤坏死因子受体2(+676)位点的等位基因及基因型频率;应用酶联免疫吸附法测定各组血浆可溶性肿瘤坏死因子受体2水平。同时结合其基因型综合分析冠心病各临床分型与血浆可溶性肿瘤坏死因子受体2水平、基因型的关系及肿瘤坏死因子受体2基因型与血浆可溶性肿瘤坏死因子受体2间的关联度。结果 (1)肿瘤坏死因子受体2(+676)位点上有3种基因型,即TT、TG和GG型;(2)在冠心病组,肿瘤坏死因子受体2(+676)位点GG基因型频率(6.8%)高于对照组(4.1%),差异有统计学意义(P=0.008);冠心病组G等位基因频率高于对照组(χ2=3.993,P=0.046);(3)稳定型心绞痛组T/G等位基因频率与不稳定型心绞痛组、急性心肌梗死组相比差异有统计学意义(P<0.05),不稳定型心绞痛组与急性心肌梗死组相比差异无统计学意义;(4)在冠心病组中,血浆可溶性肿瘤坏死因子受体2水平显著高于对照组,差异有统计学意义,冠心病组3种基因型血浆可溶性肿瘤坏死因子受体2水平与对照组比较有统计学差异,但对照组和冠心病组中血浆可溶性肿瘤坏死因子受体2水平与各自的基因型和等位基因无明显关联;(5)TG+GG基因型的患者空腹血糖、总胆固醇、收缩压水平与TT基因型患者相比差异无统计学意义,且患冠心病的风险是TT型的1.648倍。结论肿瘤坏死因子受体2(+676)位点G等位基因可能是山西汉族人群冠心病发病的危险因素;可溶性肿瘤坏死因子受体2血浆水平可间接反映机体的炎症状态,用于冠心病的病情监测;可溶性肿瘤坏死因子受体2血浆水平与肿瘤坏死因子受体2基因型之间无明显的关联。

Association of Tumor Necrosis Factor Receptor 2 Polymorphism and Clinical Classification with Coronary Heart Disease

Aim To investigate the relationship between the single nucleotide polymorphism(SNP) of tumor necrosis factor receptor 2(TNFR2) gene and soluble TNFR2(sTNFR2) with coronary heart disease(CHD) in Shanxi population.Methods Two hundred and fifty CHD patients confirmed by coronary angiography(CAG) were enrolled,98 healthy subjects served as control group.CHD group was divided into stable angina pectoris(SA,n=54),unstable angina pectoris(UA,n=110) and acute myocardial infarction(AMI,n=86) according to the clinical symptom.Theclinicai information about disease history,physical examination,assistant examination and CAG of all patients were recorded.The polymorphism of TNFR2 gene(+676) was detected by the polymerase chain reaction-ligase detection reaction(PCR-LDR) and the concentration of sTNFR2 was detected by enzyme-linked immunosorbent assay(ELISA).The association of TNFR2 gene polymorphism in different clinical situation with the level of sTNFR2 were analysed.Results(1)On 676 site,there were three genotypes: TT,TG and GG.(2)The frequency of GG type and G allele were significantly different between CHD and control(P<0.05).(3)Compared with UA and AMI group,the frequency of T/G allele was decreased in SA group(P<0.05),but no difference was found between UA and AMI group.(4)The levels of sTNFR2 were signifieantly higher in CHD patients than controls(P<0.05);In three genetypes of CHD patients the levels of sTNFR2 were increased compared with control group,but in both CHD group and control group the relation betwean levels of sTNFR2 and TG genotype and G allele were not found.(5)Although no differences were found in blood glucose,total cholesterol and systolic blood pressure between TG+GG type and TT type,the risk of patients with TG+GG type suffer from CHD was 1.648 times of those patients with TT type.Conclusions The TG+GG genetype confers independent risk factor of CHD in Han nationality population in Shanxi Province.Levels of sTNFR2 can reflect the body’s inflammatory state for monitoring CHD.There is no relationship between level of sTNFR2 and genetype.