We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC.
- Authors
Kruk, Beata; Liebe, Roman; Milkiewicz, Małgorzata; Wunsch, Ewa; Raszeja-Wyszomirska, Joanna; Lammert, Frank; Milkiewicz, Piotr; Krawczyk, Marcin
- Abstract
Background: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent major genetic risk factors for progressive liver injury in nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and chronic viral hepatitis. The aim of this study was to find out whether these variants have a detrimental impact on the progression of chronic liver disease in patients with prolonged cholestasis induced by primary sclerosing cholangitis (PSC). Methods: We prospectively recruited 178 PSC patients (112 male, age range 17–75 years, 55 with liver cirrhosis, 94 with ulcerative colitis, 48 transplanted during follow-up). PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms were genotyped using dedicated TaqMan assays. Associations between genotypes, biochemical and clinical phenotypes were analyzed using contingency tables. Results: Allele and genotype distribution of both variants were consistent with Hardy-Weinberg equilibrium. No significant differences in the genotype distribution of PNPLA3 (P = 0.90) or TM6SF2 (P = 0.72) were observed between patients with cirrhosis and patients without cirrhosis. Serum liver enzyme activities were not modified by the presence of PNPLA3 (ALT P = 0.88, AST P = 0.77) or TM6SF2 (ALT P = 0.92, AST P = 0.49) risk variants. Increasing number of risk alleles had no impact on serum liver enzyme activities, as demonstrated by a separate analysis of patients carrying 0 (n = 99), 1 (n = 64), 2 (n = 12) or 3 (n = 3) risk alleles (P>0.05). No impact of PNPLA3 or TM6SF2 risk variants was detectable in patients with PSC and ulcerative colitis, and none of the variants increased the odds of transplantation. Conclusions: Neither PNPLA3 nor TM6SF2 polymorphisms seem to contribute significantly towards an increased risk for deterioration of liver function in patients with PSC. These results underscore the divergent mechanisms of liver damage in cholestatic conditions as compared to metabolic and viral liver diseases.
- Subjects
LIVER diseases; GENETIC polymorphisms; MEMBRANE proteins; CLINICAL trials; GENETICS; DISEASE risk factors
- Publication
PLoS ONE, 2018, Vol 13, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0202942