[The cSNPs analysis in whole extron-wide of PGC-1alpha gene in Chinese population and the domain MEF2C bioinformatics study].
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.


CONCLUSIONS
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.
Lu
Wen-sheng
WS
Department of Endocrinology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021 P. R. China. lwswxqz@163.com
Yan
Xiao-dong
XD
Liu
Hong-yan
HY
Huang
Zhong
Z
Tan
Xiao-yan
XY
Huang
Qin
Q
Yang
Chuan
C
Li
Yan
Y
Yan
Li
L
Cheng
Hua
H
D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002681:China; D019295:Computational Biology / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D064326:MEF2 Transcription Factors; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D006360:Heat-Shock Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors