title: Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors.
abstract: OBJECTIVE
  There are a considerable number of patients with non-obese non-alcoholic fatty liver disease (NAFLD). However, the clinical characteristics of non-obese NAFLD is not fully understood. We investigated genetic and other clinical parameters in non-obese and obese NAFLD.
  
  
  METHODS
  The single nucleotide polymorphism rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was genotyped by the Invader assay in 540 NAFLD patients (134 non-obese and 406 obese) and 1012 control subjects (782 non-obese and 230 obese). All NAFLD patients underwent liver biopsy. Odds ratios were calculated by multiple logistic regression analysis using age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) and rs738409 genotype as explanatory variables.
  
  
  RESULTS
  Non-obese NAFLD subjects had a higher rs738409 GG genotype than obese NAFLD. Multiple logistic regression analysis indicated that the odds ratios of T2DM and rs738409 GG genotype for NAFLD were higher in non-obese than in obese groups. In non-obese NAFLD, rs738409 GG genotype was associated with lobular inflammation, hepatocyte ballooning and NAFLD activity score. In obese NAFLD, BMI and T2DM but not rs738409 GG genotype were associated with severity of histology.
  
  
  CONCLUSIONS
  We demonstrated that the risk factors for the development and progression of NAFLD were different between non-obese and obese patients and that PNPLA3 rs738409 was strongly associated with the development and progression of non-obese NAFLD.
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kessoku
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Medical Innovation, Osaka University Hospital, Osaka, Japan.
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
keywords: PNPLA3; non-alcoholic fatty liver disease; non-obese non-alcoholic fatty liver disease; type 2 diabetes mellitus