Z Gastroenterol 2019; 57(09): e278
DOI: 10.1055/s-0039-1695346
Leber und Galle
NAFLD: Donnerstag, 03. Oktober 2019, 09:40 – 11:16, Studio Terrasse 2.1 B
Georg Thieme Verlag KG Stuttgart · New York

Effects of the common PNPLA3 p.I148 M polymorphism on the fatty liver phenotypes in German patients: results from the FLAG “real life” cohort

M Krawczyk
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
2   Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Polen
,
JM Schattenberg
3   Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Deutschland
,
L Schubert
4   Gastroenterologie am Bayerischen Platz, Berlin, Deutschland
,
N Dikopoulos
5   Gastroenterologische Schwerpunktpraxis, Dornstadt, Deutschland
,
J Schwenzer
6   Bauchzentrum Biesdorf, Berlin, Deutschland
,
M Muche
7   Charité Campus Benjamin Franklin, Berlin, Deutschland
,
J Wiegand
8   Division of Gastroenterology, University Hospital Leipzig, Leipzig, Deutschland
,
G Felten
9   Gastroenterologische Praxis Herne, Herne, Deutschland
,
R Heyne
10   Leberzentrum am Checkpoint, Berlin, Deutschland
,
P Ingiliz
11   Zentrum für Infektiologie Prenzlauer Berg, Berlin, Deutschland
,
A Schmidt
12   Magen-Darm-Zentrum Wiener Platz, Köln, Deutschland
,
K Stein
13   Praxis für Infektiologie und Hepatologie Magdeburg, Magdeburg, Deutschland
,
M Manns
14   Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Deutschland
,
S Zeuzem
15   Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Deutschland
,
P Buggisch
16   IFI Institut für interdisziplinäre Medizin, Hamburg, Deutschland
17   BNG, Berufsverband Niedergelassener Gastroenterologen e.V, Deutschland
,
F Lammert
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
WP Hofmann
4   Gastroenterologie am Bayerischen Platz, Berlin, Deutschland
17   BNG, Berufsverband Niedergelassener Gastroenterologen e.V, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2019 (online)

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    Background:

    Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition commonly encountered among overweight individuals. The patatin-like phospholipase domain-containing protein (PNPLA3) p.I148 M variant is regarded as major genetic determinant of severe fatty liver phenotypes. Here we investigate the effects of this variant on fatty liver phenotype in a "real life" cohort of German NAFLD patients.

    Methods:

    All patients included in the analysis were assembled within the Fatty Liver Assessment in Germany (FLAG) program, a multicentric cohort study covering private and public outpatient clinics. The PNPLA3 p.I148 M polymorphism was genotyped using allelic discrimination assays. Its frequency was compared to a healthy control population (n = 174). The effects of PNPLA3 p.I148 M on patients' phenotypes were analysed in contingency tables and regression analyses.

    Results:

    Overall, the study cohort comprised 475 individuals (255 men) with NAFLD. Among them 185 carried the common PNPLA3 p. 148[II] genotype, while the prosteatotic p. 148[IM] and p. 148[MM] risk genotypes were present in 186 and 104 individuals, respectively. The entire FLAG cohort deviated significantly (P < 0.001) from Hardy-Weinberg equilibrium (HWE) due to the overrepresentation of the PNPLA3 risk allele. The PNPLA3 p.I148 M variant was more prevalent among FLAG patients as compared to healthy controls and increased the risk of developing NAFLD (common OR = 2.47, P = 0.005 × 10-06). It also correlated with serum AST (P = 0.043) and ALT (P = 0.011) activities. Interestingly, the presence of the PNPLA3 risk allele was associated with significantly (P < 0.001) lower serum triglyceride concentrations ([II]: 214 ± 139 mg/dl, [IM]: 186 ± 108 mg/dl, [MM]; 156 ± 76 mg/dl). Finally, the PNPLA3 p.I148 M polymorphism was associated with an increased risk of presenting with transient elastography ≥9.2 kPa (common OR = 1.50, P = 0.03), i.e. with significant fibrosis (Caballería et al. Clin Gastroenterol Hepatol 2018).

    Discussion:

    Previous genetic studies in NAFLD patients were mostly performed in tertiary academic referral centres. Here by analysing patients from a "real life" NAFLD cohort we further underscore the role of the PNPLA3 variant as the central genetic NAFLD trigger and modifier of disease severity.


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