Gallstones are formed due to a combination of genetic, metabolic, and lifestyle factors:
Genetic factors
- Variants of hepatic ATP-binding cassette transporters, such as ABCG8, have been identified as genetic susceptibility factors for gallstone disease
- Genetic variation in the promoter of uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) has been associated with gallstone formation in individuals with sickle cell disease
Metabolic factors
- High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for gallstone formation
- Factors involved in metabolic syndrome increase the risk of developing gallstones
- Dysregulation of hepatic transporters that efflux cholesterol, phospholipids, and bile salts can lead to an increased cholesterol saturation index and the formation of cholesterol crystals
Lifestyle factors
- Physical inactivity, obesity, and overnutrition are risk factors for gallstones
- Alcohol consumption has been inversely related to gallstone development
Other factors
- Neutrophil extracellular traps (NETs) have been found to play a role in the formation and growth of gallstones
- Claudin 2, a paracellular channel-forming protein, regulates paracellular ion and water flow required for proper bile composition and flow. Dysregulation of this process increases susceptibility to cholesterol gallstone disease in mice
Gallstone formation is a multifactorial process involving genetic, metabolic, lifestyle, and other factors. Understanding these factors can aid in the development of preventive strategies and therapeutic interventions for gallstone disease.