Z Gastroenterol 2018; 56(08): e255
DOI: 10.1055/s-0038-1668798
Kurzvorträge
Leber und Galle
Leber: Physiologie, Regeneration, Arzneimittelmetabolismus – Freitag, 14. September 2018, 08:15 – 09:19, 21a
Georg Thieme Verlag KG Stuttgart · New York

The PNPLA3 p.I148 M polymorphism is associated with increased liver injury in patients with polycystic ovary (PCO) syndrome

I Papapostoli
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
A Koutsou
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
P Sklavounos
2   Department of Gynecology and Obstetrics, Saarland University Hospital, Homburg, Deutschland
,
B Friesenhahn-Ochs
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
CS Stokes
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
F Lammert
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
,
M Krawczyk
1   Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
3   Laboratory of Metabolic Liver Diseases, Centre for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Polen
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

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Background:

Women with polycystic ovary (PCO) syndrome often present with advanced fatty liver disease. Previously we and others demonstrated that three critical gene variants, i.e. PNPLA3 p.I148 M, TM6SF2 p.E167K and MBOAT7 rs641738, are associated with higher hepatic fat contents and markers of chronic liver injury. Here we aim to investigate whether these variants contribute to fatty liver disease (FLD) phenotypes in the setting of PCO, as quantified non-invasively by transient elastography.

Patients and methods:

Prospectively we recruited 42 women with proven PCO (age range 18 – 53 years). The prosteatotic PNPLA3, TM6SF2 and MBOAT7 polymorphisms were genotyped using TaqMan assays. To assess hepatic fibrosis and steatosis, liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) for quantification of hepatic fat contents were obtained by elastography in fasted subjects.

Results:

The median LSM was 5.9 kPa (range 2.9 – 17.0), and the median CAP was 255 db/m (range 100 – 393). Overall, two patients presented with LSM ≥13.0 kPa, i.e. liver cirrhosis, and 18 patients showed CAp ≥280 dB/m, indicating steatosis grade ≥ S3. The PNPLA3 variant p.I148 M affected liver fibrosis: LSM differed significantly (ANOVA P = 0.022) between carriers of the risk genotype [II] (n = 15, 24%, median LSM 4.9 kPa, range 3.5 – 7.8) and genotypes [IM] (n = 22, 52%, median LSM 6.7 kPa, range 2.9 – 14.3) and [MM] (n = 5, 12%, median LSM 7.7 kPa, range 4.4 – 17.0). Overall, carriers of the risk allele [M] presented with significantly (P = 0.012) higher LSM as compared to carriers of the common genotype [II]. Compared with the frequencies in the general population (Arslanow et al. Liver Int 2016), the PNPLA3 variant was associated with an increased risk of developing PCO syndrome (common OR = 2.2, P = 0.002). Neither TM6SF2 nor MBOAT7 variants were associated with LSM or CAP, and none of the variants showed a significant association with serum liver enzyme activities.

Conclusions:

Fatty liver disease is a common feature of PCO syndrome. Carriers of the PNPLA3 risk allele are overrepresented among PCO patients and are characterized by advanced liver fibrosis. This gene variant might represent a causative link between NAFLD and PCO syndrome.