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. 2022 Dec 1;17(12):e0277084.
doi: 10.1371/journal.pone.0277084. eCollection 2022.

PNPLA3 allele frequency has no impact on biliary bile acid composition or disease course in patients with primary sclerosing cholangitis

Martti Färkkilä  1 , Hannu Kautiainen  2   3 , Andrea Tenca  1 , Kalle Jokelainen  1 , Johanna Arola  4
Affiliations

PNPLA3 allele frequency has no impact on biliary bile acid composition or disease course in patients with primary sclerosing cholangitis

Martti Färkkilä et al. PLoS One. .

Abstract

Background and aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease that leads to bile duct strictures, cholestasis, and biliary cirrhosis. PNPLA3 (patatin-like phospholipase domain containing 3), regulates cellular lipid synthesis by converting lysophosphatidic acid into phosphatidic acid. Isoleucine mutation to methionine at position 148 (I148M) causes a loss of this function. Only two studies, with contradictory results, have evaluated the role of PNPLA3 in PSC. The rs738409(G) variant of PNPLA3 has been associated with an increased risk for transplantation in male patients with dominant strictures (DS). The study aimed to evaluate the PNPLA3 allele frequency effect on the clinical outcomes, progression, and prognosis of PSC. Furthermore, we analyzed the impact of PNPLA3 on phospholipid and bile acid composition to evaluate the effect of the PNPLA3 status on UDCA response.

Patients and methods: We recruited 560 patients prospectively and collected clinical and laboratory data as well as liver histology and imaging findings. PNPLA3 (CC, CG, GG) alleles were analyzed with TaqManTM. We also analyzed bile acids (BA), cholesterol and phospholipids and individual BA from a sample aspirated during endoscopic retrograde cholangiography (ERC).

Results: Among the recruited patients, 58.4%, 35.7% and 5.9% had the wild (CC), heterozygous (CG) and homozygous (GG) alleles, respectively. The PNPLA3 haplotype did not impact bile composition or individual BA. In addition, we found no differences in age at diagnosis, disease progression, liver fibrosis or survival between the cohorts.

Conclusions: The PNPLA3 I148M variant had no significant impact on on bile composition, including UDCA content, clinical outcomes, progression of liver fibrosis, hepatobiliary cancer risk, liver transplantation, or overall survival.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Impact of PNPLA3 haplotype on the development of strictures assessed by the time to first dilatation.
Impact of the PNPLA3 haplotype; adjusted for sex and age at PSC diagnosis.
Fig 2
Fig 2. Proportion of patients who did not reach the composite end point (CCA, liver transplantation, and deaths) according to the PNPLA3 allele frequency; adjusted for sex and age at PSC diagnosis.
See this image and copyright information in PMC

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