Gallstones and Gallbladder Disease - Risk Factors

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Ethnicity

Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, Hispanics and Northern Europeans have a higher risk for gallstones than do people of Asian and African descent. People of Asian descent who develop gallstones are most likely to have the brown pigment type.

Native North and South Americans, such as Pima Indians in the U.S. and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have an 80% chance of developing gallstones during their lives, and virtually all native Indian females in Chile and Peru develop gallstones. Such cases are most likely due to a combination of genetic and dietary factors.

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Genetics

Having a family member or close relative with gallstones may increase the risk. Up to one-third of cases of painful gallstones may be related to genetic factors.

A mutation in the gene ABCG8 significantly increases a person's risk of gallstones. This gene controls a cholesterol pump that transports cholesterol from the liver to the bile duct. It appears this mutation may cause the pump to continuously work at a high rate. A single gene, however, does not explain the majority of cases, so multiple genes and environmental factors play a complex role.

Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone many not be sufficient to create gallstones. Studies indicate that the disease is complex and may result from the interaction between genetics and environment. Some studies suggest immune and inflammatory mediators may play key roles.

Diabetes

People with diabetes are at higher risk for gallstones and have a higher-than-average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to have worse infections.

Obesity and Weight Changes

Obesity. Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol, which is delivered into the bile and causes it to become supersaturated.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver, which results in supersaturation and an increased risk for gallstones.