【摘要】 目的了解中国汉族人群PGC-1α基因Thr394Thr和Gly482Ser变异与2型糖尿病的相关关系。方法招募350名中国南方汉族2型糖尿病先证者及其一级亲属,抽提外周血DNA。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析和DNA直接测序技术鉴定PGC-1α基因型。基于2型糖尿病家系,采用单倍型相对危险度分析(HRR)和传递不平衡检验(TDT)方法分析Thr394Thr和Gly482Ser变异及其单倍型与2型糖尿病的关系。结果基于2型糖尿病家系的HRR分析显示,PGC-1α基因482Ser(A)等位基因更多向子代传递(χ~2=7.2170,P=0.0072,HRR=1.4496),而Thr394Thr(G/A)等位基因在传递与未传递两组间分布频率差异无统计学意义(χ~2=2.9557,P=0.0856,HRR=0.7638)。TDT分析提示,394Thr(A)-482Ser(A)单倍型在两组间分布差异有统计学意义(χ~2=33.160,P=0.002),且与2型糖尿病呈连锁不平衡关系(χ~2=4.6841,P=0.0292)。结论 394A-482A联合变异可能增加了中国人患糖尿病的风险。更多还原

【Abstract】 Objective To investigate the relationship between Thr394Thr and Gly482Ser of the PGC-1αgene and type 2 diabetes in a family-based association study in the southern Chinese population.Methods Three hundred and fifty patients and their first-degree relatives were recruited in our study.Their blood specimens were collected to extract the genomic DNA.The genotypes of the polymorphisms Thr394Thr(G/A) and Gly482Ser(G/A) of the PGC-la gene were determined by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP) and direct sequencing.The results were analyzed by transmission disequilibrium test(TDT) and haplotype relative risk(HRR).Results HRR revealed that the 482A allele was more often transmitted to patients(χ~2 = 7.2170,P =0.0072,HRR = 1.4496).TDT analyses revealed that 394Thr(A)482Ser(A)haplotype was significantly more transmitted from heterozygous parents to patients than expected(χ~2 =33.160,P =0.002).There was a linkage disequilibrium between the haplotype and type 2 diabetes(χ~2=4.6841,P =0.0292).Conclusion The co-variation of 394A-482A may increase the risk of diabetes in the Chinese popldation.更多还原