Article Text

PDF

Experimental research
PGC-1α Gly482Ser polymorphism increases the susceptibility to NAFLD in type 2 diabetic patients
  1. Chen Yanming,
  2. Shengqing,
  3. Xixiang,
  4. Ren Zhuozhuo,
  5. Wang Manman,
  6. Zeng Longyi
  1. Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Abstract

Background and aim The aim of this study is to investigate the relationship between peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) Gly482Ser polymorphism and non-alcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2DM), and to clarify the effect of this gene variant on the transcription of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) gene.

Methods According to typical liver ultrasonographic findings, 70 NAFLD with newly-diagnosed T2DM patients, 74 NAFLD patients, 70 newly-diagnosed T2DM patients and 84 NGT subjects were recruited into this study. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyse the genotype of each individual. Then wild-type and mutated plasmids of PGC-1α were transfected respectively into liver cells and the mRNA and protein levels of PEPCK-C and PEPCK-C promoter activity were detected after transfection.

Results We demonstrated that NAFLD patients were more obese and insulin resistant. PGC-1α Ser482Ser genotype frequency and Ser482 allele frequency were higher in NAFLD patients complicated with T2DM than NGT group (p<0.05). Objects possess this genotype had lower plasma HDL-C levels but higher LDL-C levels and had higher risk for NAFLD complicated with T2DM. And the PEPCK-C mRNA and protein levels in co-transfecting PGC-1α (G) and HNF4α plasmids group increased more than PGC-1α (S) plus HNF4α group (p<0.05). Moreover, PGC-1α (G) increased PEPCK-C promoter activity with 2.0-fold and 2.2-fold versus PGC-1α (S) in HepG2 and LO2 cells respectively (p<0.05).

Conclusion PGC-1α Gly482Ser variant contributed to the onset of NAFLD in type 2 diabetic patients probably through impairing PEPCK-C gene transcription and exacerbating fat deposition.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.