Because of its multifactorial pathogenesis, it is difficult to identify human gene abnormalities that are responsible for the formation of cholesterol gallstones. Monogenic predisposition for cholelithiasis has only been ascribed to mutations in the genes in specific subgroups of patients. Table 2 summarizes human LITH genes that have been identified and updated in 2008. Missense mutations in the ABCB4 gene, which encodes the phospholipid transporter in the canalicular membrane of hepatocytes, are the basis for a particular type of cholelithiasis. The disorder is characterized by intrahepatic sludge, gallbladder cholesterol gallstones, mild chronic cholestasis, a high cholesterol/phospholipid ratio in bile, and recurrent symptoms after cholecystectomy.42,43 A defect in the ABCB4 gene could constitute the basis for this highly symptomatic and recurrent form of gallstone disease. In patients with hepatolithiasis, a common disease in Asia, low expression levels of ABCB4 and phosphatidylcholine transfer protein occur together with markedly reduced phospholipid concentrations in bile.94 In this disorder, HMG-CoA reductase activity is increased and CYP7A1 activity is reduced in gallstone patients compared with controls. Furthermore, the formation of cholesterol-rich intrahepatic stones could be induced by decreased biliary secretion of phospholipids in the setting of increased cholesterol synthesis and decreased bile salt synthesis.
Because gallbladder hypomotility favors gallstone formation, the genes for CCK and CCK-1R, which regulate gallbladder motility, are attractive candidates.54,58,59 Genetic variation in the CCK-1R gene is associated with gallstone risk, and an aberrant splicing of CCK-1R, which is predicted to result in a nonfunctional receptor, is found in a few obese patients with gallstones.95,96 However, a search for mutations or polymorphisms in the CCK-1R gene in patients with gallstones has been unsuccessful.97
Some studies have reported that certain polymorphisms of the APO-E and APO-B genes and the cholesteryl ester transfer protein, all of which are involved in carrying cholesterol in the plasma, are associated with gallstones.98-102 Although the polymorphisms in the APO-E gene have been extensively studied in patients with gallstones, results concerning the protective role of the e4 allele against gallstones have been inconsistent. The e2 allele seems to protect against gallstones, and the degree of intestinal cholesterol absorption varies with the APO-E isoform (i4>«3>«2).103 Also, the fecal excretion of cholesterol tends to be higher in persons with the APO-E2
phenotype than in those with the APO-E3 or APO-E4 phenotypes. In a study of polymorphisms at the APO-B, APO-A1, and cholesteryl ester transfer protein gene loci in patients with gallbladder disease, a polymorphism of the cholesteryl ester transfer protein gene, in relation to another HDL-lowering factor, was found to be associated with cholesterol gallstones.102 Also, there is a link between the X+ allele of the APO-B gene and an increased risk of cholesterol gallstones. A genome-wide association study in a large cohort of patients with gallstones from Germany and a linkage study in affected sib pairs identified a common variant (D19H) of the sterol transporters ABCG5 and ABCG8 on the canalicular membrane of hepatocytes as a risk factor for gallstones.104,105 It was shown to confer odds ratios of 2 to 3 in heterozygotes and 7 in homozygous carriers. This variant is also a susceptibility factor for gallstones in Chilean Hispanics, and other ABCG8 variants (T400 K, D19H, A632 V, M429 V, and C54Y) as well as ABCG5 variants (Q604E) may be important risk factors for gallstone formation in Chinese and Canadian Caucasians.106-108 This first common susceptibility gene has been predicted by QTL mapping studies in inbred mice.109
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One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.