The common adiponutrin variant p.I148M, a genetic risk factor for non-alcoholic fatty liver disease, affects fasting glucose and triglyceride levels

M Krawczyk; F Grünhage; M Mahler; S Tirziu; M Acalovschi; F Lammert

doi:10.1055/s-0030-1269564

Zeitschrift für Gastroenterologie, Table of Contents

The common adiponutrin variant p.I148M, a genetic risk factor for non-alcoholic fatty liver disease, affects fasting glucose and triglyceride levels

M Krawczyk ¹, F Grünhage ¹, M Mahler ¹, S Tirziu ², M Acalovschi ², F Lammert ¹

¹Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany, Homburg
²Department of Medicine III, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

Abstract

Aims: Last year we reported that the common adiponutrin (PNPLA3) coding polymorphism p.I148M, a genetic determinant of severe forms of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), does not increase the risk of developing gallstones (1). To date, studies on the effect of the adiponutrin variant on lipid and glucose metabolism remain controversial (2,3). Here our aim was to assess whether the PNPLA3 polymorphism p.I148M affects glucose and lipid levels in a general population.

Patients and methods: We recruited 229 individuals with gallstones (confirmed by ultrasound or cholecystectomy) from 108 families (age 24–80 years, 86% women, BMI 17–55kg/m²) and 258 gallstone-free controls (confirmed by ultrasound, age 20–70 years, 93% women, BMI 14–43kg/m²). Fasting serum glucose, triglyceride (TG) and cholesterol levels in were determined. The p.I148M polymorphism was genotyped using a PCR-based assay with 5'-nuclease and fluorescence detection. One sib from each family with gallstones (n=108) and all controls were included in the association tests.

Results: Allele were within Entrez SNP database ranges, and no deviation from Hardy-Weinberg equilibrium was detected (P >0.05). Homozygous carriers of the risk [G] allele demonstrated significantly higher (P <0.0001) median fasting glucose levels (108.0, range 80.0–315.0mg/dl) as compared to individuals with genotypes [GC] and [CC] (92.0, range 57.0–361.0mg/dl). In gallstone patients, TG levels were significantly (ANOVA P=0.032) associatted with the PNPLA3 variant ([CC] 155.0, [CG] 122.0, [GG] 104.5mg/dl); among carriers of the [C] allele, cases had significantly (P <0.01) higher TG but lower cholesterol levels as compared to controls.

Conclusions: Our results show that carriers of the risk variant are not only prone to NAFLD but also display higher serum glucose levels and point to possible role of adiponutrin in glucose homeostasis.

Literatur:

(1) Krawczyk et al., GASL 2010(2) Johansson et al., Eur J Endocrinol 2008(3) Kantartzis et al., Diabetes 2009

NASH - adiponutrin - glucose - lipids