MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis

J Gastroenterol. 2024 Jan;59(1):66-74. doi: 10.1007/s00535-023-02045-z. Epub 2023 Oct 16.

Abstract

Background: Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease. Previous genome-wide meta-analysis has identified the association between variants in TMEM163 with PBC. Here we aimed to evaluate the association between variants near the reported risk loci of TMEM163 at 2q21.3 and prognosis of PBC patients.

Methods: We performed a retrospective analysis of 347 PBC patients treated with ursodeoxycholic acid (UDCA) for at least 1 year. We collected clinical data at diagnosis and 1 year after UDCA treatment. SNPs within 200 kb upstream and downstream of the lead variant were genotyped and screened.

Results: We identified that rs661899 near MGAT5 and TMEM163 showed the strongest association with prognosis in PBC patients. Patients carrying the rs661899 T allele tended to respond incompletely to UDCA treatment and had worse performances in laboratory values including aspartate aminotransferase (53.5 vs 32 vs 28.5 U/L, p = 0.001), alkaline phosphate (157.25 vs 125 vs 113 U/L, p = 0.001), albumin (41.5 vs 42.3 vs 43.7 g/L, p = 0.008) and bilirubin (19.2 vs 14.9 vs 12.85 μmol/L, p = 0.001). GLOBE scores (p = 4.8 × 10-5) and UK-PBC risk scores (p = 4.6 × 10-4) were strongly correlated with rs661899 genotype. Patients with TT genotype had a higher risk for adverse events compared with CC genotype (p = 0.039) during the 1-year follow-up. Results were also verified in an independent cohort.

Conclusions: PBC patients carrying the rs661899 T allele are associated with poor prognosis and adverse outcomes after 1-year UDCA therapy.

Keywords: Genetic; Polymorphism; Primary biliary cholangitis; Prognosis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholagogues and Choleretics / therapeutic use
  • Cholangitis*
  • Humans
  • Liver Cirrhosis, Biliary* / complications
  • Liver Cirrhosis, Biliary* / drug therapy
  • Liver Cirrhosis, Biliary* / genetics
  • Membrane Proteins / genetics
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Ursodeoxycholic Acid
  • Cholagogues and Choleretics
  • TMEM163 protein, human
  • Membrane Proteins