Association Between Peroxisome Proliferator-activated Receptor γ Coactivator-1 Gene And Type 2 Diabetes Mellitus Of Chinese

Object Type 2 diabetes is a serious chronic disease that harm human . The development of diabetes is associated with environment and genetic factors. Peroxisome proliferator-activated receptor- r coactivator-1 (PGC-1) is a transcriptional coactivator of peroxisome proliferator activated receptor r (PPAR- r). PGC-1 plays a key role in energy homeostasis, especially in adaptive thermogenesis . In glucose metabolism, PGC-1 strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. PGC-1 also has a role in regulating expression of GLUT4 in skeletal muscle by interacting with the transcription factor MEF2C. So PGC-1 is a candidate for a susceptibility gene for type 2 diabetes mellitus and obesity. Recent studies on the relationship between the polymorphsim of PGC-1 and type 2 diabetes show that the Gly482Ser polymorphsim was more frequent among type 2diabetes than among glucose tolerant subjects. This study reported the mutation analysis of the 8 extron of PGC-1 gene and identified a Gly482Ser variant, which was associated with type 2 diabetes mellitus. We also detect the expression of PGC-lmRNA in rectus abdominis of patients with type 2 diabetes mellitus and patients with normal glucose tolerance.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype of PGC-1 gene Gly482Ser variant in 154 patients with type 2 diabetes mellitus and 130 individuals with normal glucose tolerance (NGT) . Semi-quantitative reverse transcription-polymerase chain reaction was used to assess the expression of PGC-lmRNA in rectus abdominis of patients with type 2 diabetes mellitus and patients with normal glucose tolerance. Automatic biochemistry analyzer was used to detect cholesterol ( Teh) , triglycerides(TG), high-density lipoproteir cholesterol (HDL-C) ,low-density lipoprotein cholesterol (LDL-C) and fasting plasma glucose(FPG).Result (1) The allele frequency of type 2 diabetes mellitus group was significantlydifferent from that of NGT (P<0.05) . The odd ratio for the Ser allele carrier with type 2 diabetes was 1.731(95%CI 1.240~2.417). (2) Analysis of variance revealed that Lp(a) variables were influenced by PGC-1 Gly482Ser gene variant (P<0.05) . (3) PGC-1 mRNA level was not significantly changed in type 2 diabetes mellitus compare to NGT.Conclusion The PGC-1 gene Gly482Ser variant is associated with type 2 diabetes mellitus in Hubei Chinese. Insulin resistance may be initiated in the adipose tissue, the skeletal muscle insulin resistance may be due to an impaired endocrine dysfunction by the adipose tissue.