PGC-1α基因多态性与2型糖尿病的相关性

目的 了解华南汉族人群PGC-1αt基因单核苷酸多态性与2型糖尿病的相关性.方法 采集350例2型糖尿病患者和其父母以及366名正常糖耐量志愿者的血样,提取基因组DNA.应用PCR.限制性片段长度多态性(RFLP)和DNA直接测序技术鉴定PGC-1α基因多态性位点的基因型.应用病例.对照方法和基于家庭的单倍型相对危险度分析(HRR)和传递不平衡检验(TDT)方法分析相关多态性及其单倍型与2型精尿病的相关性.结果 (1)病例-对照研究显示Gly482Ser(G/A)多态性G、A等位基因在2型糖尿病组和正常糖耐量组分布频率分别为0.589、0.411和0.687、0.313(x2=15.076,P<0.01).Thr394Thr(G/A)、Thr528Thr(A/G)和Thr612Met(C/T)等位基因在两组间分布频率差异无统计学意义(均P>0.05).394A-482A-528A单倍型在两组间分布差异有统计学意义(x2=40.2,P<0.05),且与2型糖尿病存在连锁不平衡(t=2.503,P<0.05).(2)基于家庭研究显示PGC-1α基因Gly482Ser变异的A等位基因由父母更多地向患者传递(x2=7.217,P=0.007,HRR=1.450),TDT-ETDT结果均显示482位点A等位基因由杂合子父母传递给患病子代的频率偏离0.5(均P<0.05),单倍型TDT分析显示394A-482A-528A.612C,394A-482A-528A-612T,394A-482A-528G-612C和394A-482A-528G-612T单倍型分布频率显著偏离0.5(P<0.05或P<0.01).结论 Gly482Ser(G/A)变异与华南汉族2型糖尿病的易感性密切相关,Thr394Thr(G/A)变异可能辅助了这种作用.

Association of PGC-1α gene polymorphism with type 2 diabetes mellitus

Objective To investigate the association of PGC-1 α gene single nucleotide polymorphisms (SNPs) with type 2 diabetes mellitus in Southern China Han population. Methods 350 patients with type 2 diabetes mellitus and their parents and 366 normal Han volunteers were recruited in the study. Their blood specimens were collected to extract the genornic DNA. Thr394Thr(G/A), Gly482Ser(G/A), Thr528Thr(A/G) and Thr612Met (C/T) genotypes were identified by PCR-RFLP and DNA direct sequencing. The possible association was analyzed between diabetic patients with the specific cSNPs and their haplotypes by case-control and haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods. Results (1) The case- control study indicated that G and A allele frequencies of PGC-1 α gene Gly482Ser variant were 0.589, 0.411 in type 2 diabetic group and 0.687, 0.313 in normal group respectively (X<'2> = 15.076, P < 0.01). The allele frequencies of Thr394Thr, Thr528Thr, Thr612Met polymorphisms did not show significant difference between two groups respectively (all P > 0.05). The distributions of Thr394Thr-Gly482Ser-Thr528Thr haplotypes in the diabetic group were significanly different from the controls (X<'2> = 40.2, P < 0.05) and had a linkage disequilibrium with type 2 diabetes mellitus (t = 2.503, P < 0.05). (2) The family-basod studies showed that 482A allele was transmitted more significantly both via TDT and extended TDT from heterozygous parents to patients than expected respectively (all P < 0.05). HRR also supported that the 482A allele was more often transmitted to patients than predicted by chance (X<'2> = 7.217, P = 0.007, HRR = 1. 450). TDT analyses of haplotypes suggested that the frequencies of 394A-482A-528A-612C,394A-482A-528A-612T, 394A-482A-528G-612C and 394A-482A-528G- 612T haplotypes significantly deviated from 0.5 (P < 0.05 or P < 0.01). Conclusion In Southern China Han population, type 2 diabetes mellitus is associated with the Gly482Ser variant of PGC-1α gene, and Thr394Thr (G/ A) variant of PGC-1α gene appears to play an auxiliary role in this association.