title: [Study of the 482G/A variation in PGC-1alpha gene domain MEF2C as possible mechanism of type 2 diabetes].
abstract: OBJECTIVE
  To investigate the association of the 482G/A polymorphism of the PGC-1alpha gene with type 2 diabetes by family-based study in the Han population in South China, and to analyze the quantitative and qualitative binding force changes between the PGC-1alpha domain mutant and MEF2C, as well as to evaluate the possibility of PGC-1alpha -MEF2C-GLUT4 pathway in the pathogenesis of type 2 diabetes.
  
  
  METHODS
  Blood samples were collected from 350 patients with type 2 diabetes and their first-degree relatives. Genomic DNA was extracted and polymorphic PGC-1alpha genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequencing. The results were analyzed by family-based transmission disequilibrium test (TDT) and haplotype relative risk (HRR). The protein-protein interaction between PGC-1alpha and MEF2C was detected by means of the site-directed mutagenesis kit and bacteriomatch two-hybrid system kit.
  
  
  RESULTS
  In the family-based study, HRR analyses demonstrated that the 482A allele was more often transmitted to patients than predicted by chance (chi (2)= 7.2170, P= 0.0072, HRR= 1.4496). TDT-extended test(ETDT) analyses also revealed that PGC-1alpha 482A allele was significantly deviated from 0.5 from heterozygous parents to patients than expected (219 trios, P= 0.0310; 350 trios, P= 0.0292). BacterioMatch Two-Hybrid System showed that 482A variation could lead to decreased binding force between PGC-1alpha and MEF2C (62.1+/- 8.97, P< 0.05).
  
  
  CONCLUSIONS
  The 482A polymorphism increases the risk of developing type 2 diabetic mellitus in the South China Han population, which might be mediated by the PGC-1alpha -MEF2C-GLUT4 pathway.
authors.affiliation: Department of Endocrinology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021 P. R. China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yan
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Hu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
mesh_terms: D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D026161:MADS Domain Proteins / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors; D008297:Male; D008875:Middle Aged; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D051275:Glucose Transporter Type 4; D006360:Heat-Shock Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors