title: The PNPLA3 I148M polymorphism is associated with insulin resistance and nonalcoholic fatty liver disease in a normoglycaemic population.
abstract: OBJECTIVE
  The adiponutrin/patatin-like phospholipase-3 (PNPLA3) I148M polymorphism has recently been found to contribute to differences in hepatic lipid content. Nonalcoholic fatty liver disease (NAFLD) has recently been considered a hepatic component of insulin resistance and a risk factor in the emergence of type 2 diabetes. However, whether there is an association between PNPLA3 I148M and insulin resistance and NAFLD in a normoglycaemic population is still unknown.
  
  
  METHODS
  This study enrolled 156 normoglycaemic individuals with NAFLD and 723 controls. All participants received complete biochemical and clinical workups including liver ultrasonography. They were then genotyped for the PNPLA3 I148M polymorphism.
  
  
  RESULTS
  We found significant differences in the genotype and the dominant model of the PNPLA3 I148M polymorphism between the NAFLD groups and the controls (P=0.018 and P=0.01 respectively). Furthermore, there was a dose effect of the PNPLA3 I148M genotype, in that CG heterozygotes had a risk of NAFLD between CC and GG homozygotes [adjusted odds ratio (OR)=2.03, 95% confidence interval (CI)=1.23-3.375 for the GG genotype and adjusted OR=1.55, 95% CI=1.02-2.35 for the CG genotype]. The dominant model of the PNPLA3 I148M polymorphism showed higher waist circumference, fasting insulin, Homeostasis Model Assessment (HOMA-IR), alanine aminotransferase concentrations and ferritin level. Multivariate analysis showed the PNPLA3 I148M polymorphism to be independently and significantly associated with NAFLD in our normoglycaemic participants.
  
  
  CONCLUSIONS
  This study reports an association between the PNPLA3-I148M polymorphism and insulin resistance and NAFLD in a normoglycaemic population.
authors: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors: Chih-Wen
authors: CW
authors: Wang
authors: Hsing-Yi
authors: HY
authors: Lin
authors: Shyi-Jang
authors: SJ
authors: Shin
authors: Ming-Lung
authors: ML
authors: Yu
authors: Zu-Yau
authors: ZY
authors: Lin
authors: Chia-Yen
authors: CY
authors: Dai
authors: Jee-Fu
authors: JF
authors: Huang
authors: Shinn-Cherng
authors: SC
authors: Chen
authors: Steven Shoei-Lung
authors: SS
authors: Li
authors: Wan-Long
authors: WL
authors: Chuang
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005234:Fatty Liver / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000201:enzymology*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014463:Ultrasonography; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent