哮喘病人TNF-α-308位点A/G基因多态性及mRNA表达与代谢综合征的关系

Association of TNF-alpha gene G-308A polymorphism and mRNA expression with metabolic syndrome in asthmatic patients

目的:探讨哮喘病人TNF-α-308位点的基因多态性及mRNA表达与代谢综合征(MS)的关系。方法:根据是否合并MS将124例哮喘病人分为哮喘并MS组48例和哮喘非MS组76例,选择健康志愿者60例为对照组。采用聚合酶链反应-限制性片段长度多态性分析方法测定TNF-α-308位点基因多态性,实时荧光定量PCR法检测其外周血单个核细胞中TNF-αmRNA表达水平。同时测定生化指标及受试者肺功能。结果:(1)哮喘并MS组与对照组比较,GA+AA基因型频率及A等位基因频率明显升高(P<0.05);(2)哮喘组GA+AA基因型组与GG基因型组比较,舒张压、腰围、体重指数、TG、LDL-C、HOMA-IR、IgE、CRP、TNF-α水平明显升高(P<0.05~0.01);TNF-αmRNA表达明显增加(P<0.01),FEV1%和FEV1/FVC%明显下降(P<0.01);(3)多因素回归分析结果显示,TNF-αmRNA表达与CRP、TNF-α、腰围及FINS呈正相关(t=2.100~3.932,P<0.05~0.01);HOMA-IR与LDL-C、TNF-α-308A等位基因携带呈正相关(t=7.156、7.555,P<0.01),与FEV1/FVC呈负相关(t=-4.063,P<0.01);FEV1%与IgE、FINS、TNF-α呈负相关(t=-3.639^-5.644,P<0.01)。结论:哮喘病人TNF-α-308位点G→A变异及TNF-αmRNA表达增加与哮喘病人的代谢表型有关。TNF-α-308位点A等位基因携带、LDL-C水平增加及肺功能下降导致胰岛素抵抗,进而造成哮喘病人代谢综合征的发生率增加。

Objective：To explore the relationship between gene TNF-α G-308A polymorphism,mRNA expression and the Metabolic Syndrome（MS） in asthmatic patients.Methods：We recruited 124 asthmatic patients,who were separated into asthma with MS/asthma without MS groups.Genomic DNA was extracted from peripheral blood mononuclear cells of asthmatics and 60 healthy controls.Single nucleotide polymorphism of TNF-α-308 locus was genotyped using PCR-RFLP.TNF-α mRNA expression was analyzed by qRT-PCR.Some biochemical variables were determined and lung functions were also examined.Results：（1） Group of asthma with MS displayed a greater prevalence in AA＋GA genotypes and allele A frequency than control group（P0.05）.（2） In the group of asthma,the diastolic blood pressure,waist circumference,body mass index（BMI）,serum TG,LDL-C,HOMA-IR,IgE,CRP,TNF-α,and the TNF-α mRNA expression were significant higher（P0.05-0.01）,but FEV 1 % and FEV 1/FVC% of lung function were lower（P0.01） in genotypes GA＋AA group compared with the genotype GG group.（3） Further multivariate regression analysis revealed that TNF-α mRNA expression had positive correlation with CRP,TNF-α,waist circumference and FINS levels（t = 2.100-3.932,P0.05-0.01）.Our result also showed that HOMA-IR had positive correlation with LDL-C,TNF-α-308 A carrier（t = 7.156,7.555,P0.01）,but had negative correlation with FEV1/FVC（t =-4.063,P0.01）.Also,there were negative correlation between FEV 1 % and IgE,FINS,and TNF-α（t =-3.639--5.644,P0.01）.Conclusion：Our data suggested that TNF-α-308 G→ A variation and its increased mRNA expression are related to metabolic phenotype in asthma patients.Carrier of TNF-α-308A locus,high level of LDL-C and decrement in lung function lead to insulin resistance.Thus,it results in an increased incidence of metabolic syndrome in asthmatic patients.