Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses

Hum Genomics. 2024 Feb 12;18(1):19. doi: 10.1186/s40246-024-00583-y.

Abstract

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

Keywords: Campesterol; Cholecystitis; Cholelithiasis; Colocalization analysis; Genome-wide association study; Mendelian randomization; Risk factor.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics
  • Cholecystitis* / epidemiology
  • Cholecystitis* / genetics
  • Cholesterol / analogs & derivatives*
  • Gallstones* / epidemiology
  • Gallstones* / genetics
  • Gallstones* / metabolism
  • Humans
  • Lipoproteins / genetics
  • Mendelian Randomization Analysis
  • Phytosterols*

Substances

  • campesterol
  • Lipoproteins
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • Phytosterols
  • Cholesterol
  • ABCG8 protein, human
  • ABCG5 protein, human