title: The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study.
abstract: BACKGROUND
  Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population.
  
  
  METHODS
  Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18-70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-α 227 ALA, PPAR-γ pro 12 ALA, SOD2 C47T, and LOX-1 IVS4-14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument.
  
  
  RESULTS
  Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5-218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005).
  
  
  CONCLUSIONS
  The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.
authors.affiliation: Departments of aGastroenterologybGeneticscHealth Public and Epidemiology, Gulhane School of Medicine, AnkaradDepartment of Gastroenterology, Marmara University, IstanbuleDepartment of Gastroenterology, Katip Çelebi University, Izmir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Uygun
authors.forename: Kadir
authors.initials: K
authors.lastname: Ozturk
authors.forename: Hakan
authors.initials: H
authors.lastname: Demirci
authors.forename: Ali
authors.initials: A
authors.lastname: Oztuna
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.forename: Salih
authors.initials: S
authors.lastname: Kozan
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Yilmaz
authors.forename: Omer
authors.initials: O
authors.lastname: Kurt
authors.forename: Turker
authors.initials: T
authors.lastname: Turker
authors.forename: Sezgin
authors.initials: S
authors.lastname: Vatansever
authors.forename: Emrah
authors.initials: E
authors.lastname: Alper
authors.forename: Belkis
authors.initials: B
authors.lastname: Unsal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008049:Lipase / Q000097:blood / Q000235:genetics; D008099:Liver / Q000473:pathology; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D055815:Young Adult; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent