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. 2002 Jun;235(6):842-9.
doi: 10.1097/00000658-200206000-00012.

Gallstones: genetics versus environment

Attila Nakeeb  1 , Anthony G Comuzzie, Lisa Martin, Gabriele E Sonnenberg, Debra Swartz-Basile, Ahmed H Kissebah, Henry A Pitt
Affiliations

Gallstones: genetics versus environment

Attila Nakeeb et al. Ann Surg. 2002 Jun.

Abstract

Objective: The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones.

Summary background data: Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined.

Methods: A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease.

Results: In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease.

Conclusions: These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

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Figures

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Fig. 1. Prevalence of gallstone by family history in the association study.
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Fig. 2. Prevalence of gallstone disease in the family study.
See this image and copyright information in PMC

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