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DOI: 10.1055/s-0039-1695346
Effects of the common PNPLA3 p.I148 M polymorphism on the fatty liver phenotypes in German patients: results from the FLAG “real life” cohort
Publikationsverlauf
Publikationsdatum:
13. August 2019 (online)
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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