title: Genetic variation in the patatin-like phospholipase domain-containing protein-3 (PNPLA-3) gene in Asian Indians with nonalcoholic fatty liver disease.
abstract: BACKGROUND
  The association of the rs738409 polymorphism of patatin-like phospholipase-3 (PNPLA3) with nonalcoholic fatty liver disease (NAFLD) has been suggested in other populations, but not in Asian Indians. We investigated the association of the rs738409 polymorphism of PNPLA3 with clinical, anthropometric, and biochemical profiles in Asian Indians with NAFLD.
  
  
  METHODS
  In this case-control study, 162 cases and 173 controls were recruited. Abdominal ultrasound, clinical, anthropometry, and biochemical profiles were determined. Fasting insulin levels and values for homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Polymerase chain reaction and restriction fragment length polymorphism of the PNPLA3 gene were performed. The associations of this polymorphism with clinical, anthropometric, and biochemical profiles were investigated.
  
  
  RESULTS
  A higher frequency of C/G and G/G genotypes of the rs738409 polymorphism was obtained in cases as compared to controls (P=0.04), and as a consequence the frequency of the minor allele G was significantly higher in cases (P=0.003). In this study, the G allele was associated with significantly higher fasting insulin (P=0.002), HOMA-IR (P=0.05), alanine transaminase (P=0.003), and aspartate transaminase (P=0.04) values only in cases, but not in the controls. The values of serum triglycerides and total cholesterol were slightly higher in cases with G/C+G/G genotypes but statistically not significant (P>0.05). Using a multivariate logistic regression model after adjusting for age, sex, body mass index, and fasting insulin, subjects with the G/G genotype showed higher risk of NAFLD [odds ratio (OR), 1.98, 95% confidence interval (CI) 1.43-2.73, P=0.04). The relationships of the rs738409 polymorphism with the metabolic parameters were not significant after adjustment for multiple comparisons.
  
  
  CONCLUSIONS
  Asian Indians in north India carrying the allele rs738490 of PNPLA3 is predispose to develop NAFLD.
authors.affiliation: 1 Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences , New Delhi, India .
authors.forename: Surya Prakash
authors.initials: SP
authors.lastname: Bhatt
authors.forename: Priyanka
authors.initials: P
authors.lastname: Nigam
authors.forename: Anoop
authors.initials: A
authors.lastname: Misra
authors.forename: Randeep
authors.initials: R
authors.lastname: Guleria
authors.forename: Ravindra Mohan
authors.initials: RM
authors.lastname: Pandey
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000328:Adult; D000886:Anthropometry; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004247:DNA / Q000235:genetics; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007194:India / Q000453:epidemiology; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000000981:diagnostic imaging; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000235:genetics; D050177:Overweight / Q000150:complications / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D008076:Cholesterol, HDL; D004247:DNA; D008049:Lipase; D008565:Membrane Proteins; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent