title: Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus.
abstract: OBJECTIVE
  A genome-wide association study revealed that the single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent pilot studies investigated the effects of dipeptidyl peptidase-4 inhibitors on liver function and glucose metabolism in NAFLD with type 2 diabetes mellitus (DM). We herein evaluated the efficacy of alogliptin in NAFLD patients with type 2 DM as well as the relationship between genotypes at rs738409 in PNPLA3 and treatment efficacy.
  
  
  METHODS
  Forty-one biopsy-proven NAFLD patients with type 2 DM treated with 25 mg/day alogliptin were retrospectively enrolled. SNP rs738409 in PNPLA3 was present in all patients. Clinical data were measured before and after the treatment.
  
  
  RESULTS
  Average hemoglobin A1c (HbA1c) levels mostly remained unchanged. Moreover, significant changes were not noted in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the follow-up period. A positive correlation was observed between improvements in HbA1c (ΔHbA1c) levels and changes in AST (ΔAST) and ALT (ΔALT) levels (r = 0.325 and 0.439, respectively). Patients with the risk allele (G-allele) showed more positive correlation between ΔHbA1c and changes in transaminase. Furthermore, improvements in the levels of total cholesterol, triglycerides and hyaluronic acid were significantly greater in G-allele patients in the weight loss group.
  
  
  CONCLUSIONS
  The treatment of NAFLD with type 2 DM with alogliptin contributed to the amelioration of NAFLD. Our results suggested that differences in the PNPLA3 risk allele affected the therapeutic effects of this treatment.
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kan
authors.affiliation: Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuhara
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Naeshiro
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Yohji
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hiramatsu
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.affiliation: Department of Gastroenterology Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
keywords: alogliptin; non-alcoholic fatty liver disease; patatin-like phospholipase 3 single nucleotide polymorphism; type 2 diabetes mellitus