Objective: To analyze distribution characteristics of PGC-1alpha gene coding single nucleotide polymorphisms (cSNPs), and to investigate the association between cSNPs and type 2 diabetes mellitus, and to study biological information about PGC-1alpha domain muscle enhancer factor 2C (MEF2C) in Chinese Han population.
Methods: These cSNPs were identified by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA direct sequencing technology in a total of 263 type 2 diabetic patients and 282 normal glucose tolerant controls. The possible association was analyzed between type 2 diabetes mellitus and the specific cSNPs and their haplotypes by case-control method. The tertiary structure of PGC-1alpha domain MEF2C was predicated and analyzed for possible biological information by a series of bioinformatics soft wares.
Results: Four variants were found in whole extron-wide of PGC-1alpha gene in Chinese Han diabetic population. They were 394G/A, 482G/A, 528A/G and 612C/T. The 482G/A polymorphism was remarkably associated with type 2 diabetes (chi2 = 14.2025, P= 0.0002). Haplotypes analysis shown that distribution frequency of haplotypes had a statistical difference between type 2 diabetes mellitus and normal glucose tolerance control groups (chi2 = 59.9, P< 0.01) and haplotype 394A-482A-528A had a linkage disequilibrium with type 2 diabetes (t= 2.361, P< 0.05). The tertiary simulant structure of PGC-1alpha domain MEF2C was established successfully by computer. The 482G/A variant accompanied with hydrogen bonds breaking might decrease hydrophobicity and lead to an incompact space configuration which was very critical to function.
Conclusion: The 482G/A variant could decrease binding force between PGC-1alpha and MEF2C and increase the risk of type 2 diabetes in Chinese Han population by PGC-1alpha -MEF2C-GLUT-4 pathway.