【摘要】 目的研究过氧化物酶增殖激活受体γ共激活子1α(peroxisomeproliferatorsactivatedreceptorγcoactivator1α,PGC1α)基因单核苷酸多态性(singlenucleotidepolymorphism,SNP)与2型糖尿病(type2diabetesmellitus,T2DM)的关联性。方法应用聚合酶链反应限制性内切酶片段长度多态性技术,选择PGC1α基因4个常见SNPs位点:Thr394Thr(ACG→ACA)、Gly482Ser(GGT→AGT)、Thr612Met(ACG→ATG)和IVS2+52C→A,对69个T2DM家系(310例)进行基因分型,并用传递不平衡检验(transmissiondisequilibriumtest,TDT)和同胞传递不平衡检验(sibtransmissiondisequilibrium,STDT)进行分析。用同样方法在无家族史的156例T2DM患者及111名糖耐量正常者中进行病例对照关联分析,检验Gly482Ser多态性在散发人群中的分布。结果(1)经TDTSTDT检验,未发现单个PGC1α基因SNPs位点在T2DM患病子代中优势传递;(2)在病例对照关联分析中,Gly482Ser位点多态性在两组人群的分布差异有统计学意义,携带者GA基因型罹患T2DM的危险性可增加1.85倍,且等位基因在两组人群的分布差异有统计学意义(P=0.046);(3)在无家族史的糖耐量正常者中,Gly482Ser位点的GG基因型的高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯水平与GA+AA基因型比较,差异有统计学意义(分别为P=0.043,P=0.046,P=0.037)。结论PGC1α基因Gly482Ser多态性可能与T2DM的易感性相关。更多还原

【Abstract】 Objective To observe the association between single nucleotide polymorphism (SNP) of peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) gene and type 2 diabetes mellitus(T2DM). Methods Four common SNPs of PGC-1α gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and then analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 69 T2DM pedigrees (310 individuals). Furthermore, the authors performed a case-control study to genotype Gly482Ser in 156 patients with T2DM and 111 normal glucose tolerance people without family history. Results (1)There were no positive results in four variances in TDT-STDT analysis(P>0.05). (2)The Gly482Ser exhibited a significant difference between the two groups. GA genotype carriers were at increased risk for T2DM (OR=1.85), and there was statistically significant difference in the allele frequency between the case and control groups(P=0.046). (3) The subjects with GG genotype at position Gly482Ser had a higher HDL-C and lower LDL-C and TG levels when compared against those with GA+AA genotype in the control group without family history(P=0.043,P=0.046,P=0.037 respectively). Conclusion This study suggested that the PGC-1α gene might be implicated in the pathogenesis of T2DM. But the studied SNPs in PGC-1α gene may not be major susceptibility ones of T2DM mellitus in Han people of Shanghai.更多还原