The cSNPs analysis in whole extron-wide of PGC-1alpha gene in Chinese population and the domain MEF2C bioinformatics study / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 409-416, 2007.
Artigo
em Chinês
| WPRIM
| ID: wpr-247305
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fatores de Transcrição
/
Polimorfismo de Fragmento de Restrição
/
Dados de Sequência Molecular
/
Modelos Moleculares
/
Modelos Logísticos
/
Química
/
China
/
Reação em Cadeia da Polimerase
/
Sequência de Aminoácidos
/
Homologia de Sequência de Aminoácidos
Tipo de estudo:
Estudo prognóstico
/
Fatores de risco
Limite:
Idoso
/
Feminino
/
Humanos
/
Masculino
País/Região como assunto:
Ásia
Idioma:
Chinês
Revista:
Chinese Journal of Medical Genetics
Ano de publicação:
2007
Tipo de documento:
Artigo
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