Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors

Yasushi Honda; Masato Yoneda; Takaomi Kessoku; Yuji Ogawa; Wataru Tomeno; Kento Imajo; Hironori Mawatari; Koji Fujita; Hideyuki Hyogo; Takato Ueno; Kazuaki Chayama; Satoru Saito; Atsushi Nakajima; Kikuko Hotta

doi:10.1111/hepr.12648

Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors

Hepatol Res. 2016 Sep;46(10):1011-8. doi: 10.1111/hepr.12648. Epub 2016 Apr 5.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
² Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan.
³ Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
⁴ Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
⁵ Department of Medical Innovation, Osaka University Hospital, Osaka, Japan.

PMID: 26763865
DOI: 10.1111/hepr.12648

Abstract

Aim: 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.

Conclusion: 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.

Keywords: PNPLA3; non-alcoholic fatty liver disease; non-obese non-alcoholic fatty liver disease; type 2 diabetes mellitus.