The rs626283 Variant in the MBOAT7 Gene is Associated with reduced survival in primary biliary cholangitis

Background & Aims:

Primary biliary cholangitis is a chronic cholestatic liver disease. Its occurrence is influenced by genetic and environmental factors. Recently, the rs626283 polymorphism in the MBOAT7 gene has been found to be associated with adverse outcome in patients with alcoholic liver disease and NAFLD in adults. We aimed to evaluate the influence of the MBOAT7 risk variant in a cohort of patients with primary biliary cholangitis.

Methods:

This is an analysis of a single-center cohort of patients with primary biliary cholangitis at the University Hospital Heidelberg. The rs626283 polymorphism in the MBOAT7 gene was evaluated with regard to clincal characteristis and outcome.

Results:

The final cohort comprises 123 patients with primary biliary cholangitis. 114 (92.7%) were female and 102/123 (82.9%) AMA positive. The median age at entry into the study was 49.2 years. 35/123 (28.5%) patients were wildtype, 65/123 (52.8%) patients were heterozygous and 23/123 (18.7%) patients carried the mutant MBOAT7 gene. Patients with homozygous mutant allele oft the MBOAT7 gene developde significantly more HCC (3/23 (13.0%) vs. 2/100 (2.0%); p = 0.02) and had signifcantly worse clinical outcome (death: 5/23 (21.7%) vs. 8/100 (8.0%); p = 0.05; OLT: 8/23 vs. 12/100 (12.0%); p = 0.007; death/OLT: 10/23 (43.5%) vs. 15/100 (15.0%); p = 0.003). Transplantation-free-survival was significantly reduced in patients with homozygous mutant allele oft the MBOAT7 gene (16.2 years vs. 25.4 years; log-rank: p = 0.003). In multivariate analysis including age, gender, UDCA dosing, MBOAT7 (p = 0.009) was the only risk factor associated independently with reduced transplantation-free survival.

Conclusion:

In this single-center cohort we identified the rs626283 polymorphism in the MBOAT7 gene as an independent risk factor for reduced transplantation-free survival in patients with primary biliary cholangitis.