Study of the 482G/A variation in PGC-1alpha gene domain MEF2C as possible mechanism of type 2 diabetes.
- Author:
Wensheng LU
1
;
Xiaodong YAN
;
Qin HUANG
;
Yingyu HU
;
Mei ZHONG
;
Zhong HUANG
;
Hui CHEN
;
Hua CHENG
Author Information
- Publication Type:Journal Article
- MeSH: Asian Continental Ancestry Group; genetics; Diabetes Mellitus, Type 2; genetics; metabolism; Ethnic Groups; genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Glucose Transporter Type 4; metabolism; Haplotypes; Heat-Shock Proteins; genetics; metabolism; Humans; Logistic Models; MADS Domain Proteins; genetics; metabolism; MEF2 Transcription Factors; Male; Middle Aged; Myogenic Regulatory Factors; genetics; metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polymorphism, Single Nucleotide; genetics; Protein Structure, Tertiary; genetics; Signal Transduction; Transcription Factors; genetics; metabolism; Two-Hybrid System Techniques
- From: Chinese Journal of Medical Genetics 2008;25(6):616-623
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSBlood 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.
RESULTSIn 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).
CONCLUSIONThe 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.
