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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。
Objective To investigate the association between single nucleotide polymorphism (SNP) of peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) gene and type 2 diabetes mellitus (T2DM). Methods Four common SNPs of PGC1α gene were selected by polymerase chain reaction restriction fragment length polymorphism (PCR): Thr394Thr (ACG → ACA), Gly482Ser (GGT → AGT), Thr612Met (ACG → ATG) and IVS2 + 52C → A, genotyped 69 T2DM pedigrees (310 patients), and analyzed by transmissiondisequilibriumtest (TDT) and sibtransmissiondisequilibrium (STDT). Case-control analysis was performed in 156 T2DM patients without familial history and 111 normal glucose tolerance patients by the same method to test the distribution of Gly482Ser polymorphism in the sporadic population. Results (1) No single PGC1α gene SNPs was found to be predominantly transmitted in the offspring of T2DM patients by TDTSTDT test. (2) In the case-control analysis, the distribution of Gly482Ser polymorphism in the two groups was Statistical significance, carrier GA genotype risk of T2DM increased by 1.85 times, and the distribution of allele in two groups was statistically significant (P = 0.046); (3) in the absence of family history of glucose tolerance In normal subjects, the levels of GG genotypes of GG genotypes at Gly482Ser site were significantly different from those of GA + AA genotypes (P = 0.043, P = 0.046, P = 0.037). Conclusion The PGC1α gene Gly482Ser polymorphism may be related to the susceptibility of T2DM.