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

AIM:

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.

CONCLUSION:

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: Hiromi Kan, Hideyuki Hyogo, Hidenori Ochi, Kikuko Hotta, Takayuki Fukuhara, Tomoki Kobayashi, Noriaki Naeshiro, Yohji Honda, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Kazuaki Chayama
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 46 Issue 3 Pg. E146-53 (Mar 2016) ISSN: 1386-6346 [Print] Netherlands
• PMID: 26147768 (Publication Type: Journal Article)
• Copyright: © 2015 The Japan Society of Hepatology.