Genetics of gallstone disease

Area of Science:

• Gastroenterology
• Genetics
• Hepatobiliary Metabolism

Background:

• Gallstone disease (GD) is a common gastrointestinal disorder with significant healthcare costs.
• While often linked to external factors, inherited predisposition plays a crucial role in gallstone risk, particularly in adults and women.

Purpose of the Study:

• To review current knowledge on the genetic contribution to gallstone disease.
• To present recent research on the genetics of gallstone formation.

Main Methods:

• Literature review of existing data and recent research on gallstone genetics.

Main Results:

• Key gene variants, like ABCG5/G8 (p.D19H), significantly predispose individuals to gallstones.
• Loss-of-function mutations in ABCB4 can cause low phospholipid-associated cholelithiasis.
• Gallstones, primarily cholesterol stones, form due to bile supersaturation, a consequence of various risk factors.

Conclusions:

• Gallstone disease is multifactorial, with identified major genetic contributors.
• Further understanding of hepatobiliary metabolism and risk factors could enable personalized treatments and lifestyle interventions, potentially reducing reliance on invasive therapies like laparoscopic cholecystectomy.