Peroxisome Proliferator Activated Receptor γ Coactivator-1 (PGC-1) Gly482Ser Varition Is Associated With Type 2 Diabetes Mellitus In Chinese

Peroxisome proliferator activated receptor ( coactivator-1 (PGC-1) is a transcriptional coactivator of the nuclear receptor PPARγ, a transcription factor involved in adipogenesis and a functional receptor for thiazolindinediones. Reduced expression of mitochondrial respiratory genes and PGC-1 has been found in individuals with type 2 diabetes mellitus. PGC-1 seems to regulate the expression of oxidative phosphorylation genes. PGC-1 has also been reported to up-regulate glucose transporter 4 and thereby increase glucose uptake in muscle. In addition, PGC-1 is involved in hepatic gluconeogenesis by increasing gene transcription of phosphoenolpyruvate carboxykinase and glucose-6- phosphatase. There is linkage between the PGC-1 genomic region on chromosome 4p15.1 and fasting serum insulin concentrations in Pima Indians. A 482 Gly→Ser substitution in PGC-1 has been reported to be associated with an increased relative risk of type 2 diabetes in the Danish and UK populations. In contrast to these reports, the Gly482Ser substitution had no effect on the risk of type 2 diabetes in French Caucasians. In the current study, we investigated whether the Gly482Ser polymorphism increased susceptibility to Chinese type 2 diabetes.Objective To investigate if the Gly482Ser substitution in the peroxisome proliferator activated receptor γ coactivator-1(PGC-1) gene is associated with type 2 diabetes mellitus in Chinese.Methods A total of 238 Dalian subjects in China were selected. 140 were type 2 diabetes and 98 were nondiabetes. Genotyping of PGC-1 was undertaken with PCR-RFLP method. Height and weight was measured. Blood lipid and glucose were determined with enzymatic method. Serum insulin was determined with radioimmunoassay (RIA) and C peptide were examined with immunoradiometric assay (IRMA).Results Gly482Ser genotype of PGC-1 were Gly/Gly 33%,Gly/Ser 52%,Ser/Ser 15% in non-diabetics and Gly/Gly 20%,Gly/Ser 51%,Ser/Ser 29% in diabetics. There were significant differences in genotypes and allele distribution between subjects with type 2 diabetes mellitus and non-diabetes ((2=8.469,P=0.014; (2=7.656,P=0.006). In non-diabetic subjects and type 2 diabetic subjects, the value of BMI, blood glucose, triglycerides, Cholesterol(Ch), HDL-Ch, insulin, C peptide did not differ between subjects with 482Ser variants and those with non-482Ser variant.Conclusion The PGC-1 Gly482Ser polymorphism might be related to the development of type 2 diabetes. There was no association between clinical variances and Gly482Ser substitution in type 2 diabetic subjects and non-diabetic subjects.