REVIEW PAPER
Genetic basis for cholecystolithiasis. Existing state of knowledge
1
Clinical Genetics Department, Medical University, Lublin, Poland
2
General Surgery Department, Independent Public Hospital and Health Care Centre in Lubartów, Poland
3
Human Anatomy Department, Medical University, Lublin, Poland
Corresponding author
Przemysław Łodej
Clinical Genetics Department, Medical University, Radziwiłłowska 11, 20-080 Lublin, Poland
Clinical Genetics Department, Medical University, Radziwiłłowska 11, 20-080 Lublin, Poland
J Pre Clin Clin Res. 2013;7(1):1-5
KEYWORDS
cholecystolithiasisCholelithiasis - geneticsCholelithiasisCholecystolithiasis - etiologyGenetic Predisposition to Disease - genetics
ABSTRACT
Introduction and objective:
The pathogenesis of cholecystolithiasis is not well recognized. It is postulated that coexistence of environmental factors with genetic factors in individuals predispose to this illness. In this study the authors present the current state of knowledge about the pathogenesis of cholecystolithiasis and predisposing genetic factors such as: genes polymorphisms, genes expression and genetic mutations.
Abbreviated description of the state of knowledge:
The obesity, the female sex, numerous pregnancies, diabetes, cirrhosis, type C hepatitis, coronary heart disease, long-term parenteral nutrition are well known risk factors. Also the polymorphisms in some genes are connected with cholecystolithiasis, for example: polymorphisms within MUC1 and MUC2 mucin genes, ABCG8 D19H gene encoding halftransporter. Mutated forms of some proteins such as: SLC10A2 (Solute Carrier Family 10 Member 2), increased expression of NPC1L1 protein (Niemann Pick C1 Like Protein 1) and ACAT2 (Acyl Coenzyme A-cholesterol Transferase), over expression of SCP2 gene (Carrier Sterol Protein 2), the mutation of the UGT1A1 gene (Uridine 5’-diphosphate-glucuronosyltransferase 1 A1) can predispose to the development of gallstones.
Summary:
The incidence of cholecystolithiasis is constantly increasing. At present this disease constitutes the most frequent cause of surgical interventions in Europe, in the USA and in Australia. The lengthened life span, the rising percentage of obese individuals, suffering from diseases associated with the progress of civilization as well as the ageing of societies may influence on the development of cholecystolithiasis.
The pathogenesis of cholecystolithiasis is not well recognized. It is postulated that coexistence of environmental factors with genetic factors in individuals predispose to this illness. In this study the authors present the current state of knowledge about the pathogenesis of cholecystolithiasis and predisposing genetic factors such as: genes polymorphisms, genes expression and genetic mutations.
Abbreviated description of the state of knowledge:
The obesity, the female sex, numerous pregnancies, diabetes, cirrhosis, type C hepatitis, coronary heart disease, long-term parenteral nutrition are well known risk factors. Also the polymorphisms in some genes are connected with cholecystolithiasis, for example: polymorphisms within MUC1 and MUC2 mucin genes, ABCG8 D19H gene encoding halftransporter. Mutated forms of some proteins such as: SLC10A2 (Solute Carrier Family 10 Member 2), increased expression of NPC1L1 protein (Niemann Pick C1 Like Protein 1) and ACAT2 (Acyl Coenzyme A-cholesterol Transferase), over expression of SCP2 gene (Carrier Sterol Protein 2), the mutation of the UGT1A1 gene (Uridine 5’-diphosphate-glucuronosyltransferase 1 A1) can predispose to the development of gallstones.
Summary:
The incidence of cholecystolithiasis is constantly increasing. At present this disease constitutes the most frequent cause of surgical interventions in Europe, in the USA and in Australia. The lengthened life span, the rising percentage of obese individuals, suffering from diseases associated with the progress of civilization as well as the ageing of societies may influence on the development of cholecystolithiasis.
REFERENCES (43)
1.
Kozicki I. Kamica pęcherzyka żołciowego. In: Szmidt J., Kużdżał J. (red.). Podstawy chirurgii. 2nd ed. Krakow, Medycyna Praktyczna, 2010; 44. p. 950–956. ISBN: 978–83–7430–228–9.
2.
Tomecki R, Dzieniszewski J, Gerke W, et al. Kamica pęcherzyka żołciowego w populacji miejskiej w Polsce. Pol Arch Med Wewn. 1995; 94(3): 243–249.
3.
van Erpecum KJ. Pathogenesis of cholesterol and pigment gallstones: An update. Clin Res Hepatol Gastroenterol. 2011; 35(4): 281–287.
4.
Harvey PR, Upadhya GA, Strasberg SM. Immunoglobulins as nucleating proteins in the gallbladder bile of patients with cholesterol gallstones. J Biol Chem. 1991; 266(21): 13996–14003.
5.
Abei M, Schwarzendrube J, Nuutinen H, et al. Cholesterol crystallizationpromoters in human bile: comparative potencies of immunoglobulins, α1-acid glycoprotein, phospholipase C, and aminopeptidase N. J Lipid Res. 1993; 34(7): 1141–1148.
6.
Lee SP, LaMont JT, Carey MC. Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. J Clin Invest. 1981; 67(6): 1712–1723.
7.
Yamashita G, Ginanni Corradini S, Secknus R, et al. Biliary haptoglobin, a potent promoter of cholesterol crystallization at physiological concentrations. J Lipid Res. 1995; 36(6): 1325–1333.
8.
Abei M, Nuutinen H, Kawczak P, et al. Identification of human biliary α1-acid glycoprotein as a cholesterol crystallization promotor. Gastroenterology. 1994; 106(1): 231–238.
9.
Kibe A, Holzbach RT, LaRusso NF, et al. Inhibition of cholesterol crystal formation by apolipoproteins in supersaturated model bile. Science. 1984; 225(4661): 514–516.
10.
Busch N, Lammert F, Matern S. Biliary secretory immunoglobulin A is a major constituent of the new group of cholesterol crystal-binding proteins. Gastroenterology. 1998; 115(1): 129–138.
11.
Miquel JF, Nunez L, Amigo L, et al. Cholesterol saturation, not proteins or cholecystitis, is critical for crystal formation in human gallbladder bile. Gastroenterology. 1998; 114(3): 1016–1023.
12.
van Erpecum KJ, Wang DQ, Lammert F, et al. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: Soluble pronucleating proteins in gallbladder and hepatic biles. J Hepatol. 2001; 35(4): 444–451.
13.
Chuang SC, Juo SH, Hsi E, et al. Multiple mucin genes polymorphisms are associated with gallstone disease in Chinese men. Clin Chim Acta. 2011; 412(7–8): 599–603.
14.
Tennert U, Tonjes A, Ruffert C, et al. Genetic analysis of associations between variants in genes conferring diet-induced gallbladder contraction and bile-salt-induced gallbladder relaxation and gallstone susceptibility in two distinct human populations. Gastroenterology. 2010; 138(5 SUPPL.1): S211.
15.
Cong P, Pricolo V, Biancani P, et al. Effects of cholesterol on CCK- 1 receptors and caveolin-3 proteins recycling in human gallbladder muscle. Am J Physiol Gastrointest Liver Physiol. 2010; 299(3): G742– G750.
16.
Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2009; 136(2): 425–440.
17.
Galman C, Miquel JF, Perez RM, et al. Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians. Gastroenterology. 2004; 126(3): 741–748.
18.
Bergheim I, Harsch S, Mueller O, et al. Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers. J Lipid Res. 2006; 47(1): 42–50.
19.
Renner O, Harsch S, Strohmeyer A, et al. Reduced ileal expression of OSTalpha-OSTbeta in non-obese gallstone disease. J Lipid Res. 2008; 49(9): 2045–2054.
20.
Renner O, Harsch S, Schaeffeler E, et al. A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PLoS One. 2009; 4(10): e7321.
21.
Jiang ZY, Jiang CY, Wang L, et al. Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients. Biochem Biophys Res Commun. 2009; 379(1): 49–54.
22.
Wang HH, Portincasa P, Mendez-Sanchez N, et al. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology. 2008; 134(7): 2101–2110.
23.
Buch S, Schafmayer C, Volzke H, et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet. 2007; 39(8): 995–999.
24.
Grunhage F, Acalovschi M, Tirziu S, et al. Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol. Hepatology. 2007; 46(3): 793–801.
25.
Rudkowska I, Jones PJ. Polymorphisms in ABCG5/G8 transporters linked to hypercholesterolemia and gallstone disease. Nutr Rev. 2008; 66(6): 343–348.
26.
Katsika D, Magnusson P, Krawczyk M, et al. Gallstone disease in Swedish twins: risk is associated with ABCG8 D19H genotype. J Intern Med. 2010; 268(3): 279–285.
27.
Stender S, Frikke-Schmidt R, Nordestgaard BG, et al. Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population. Hepatology. 2011; 53(2): 640–648.
28.
Schafmayer C, Teumer A, Buch S, et al. A genome-wide scan identifies TM4SF4 (intestine and liver tetraspan membrane protein 4) as a susceptibility locus for gallstone disease. Gastroenterology. 2010; 138(5 SUPPL.1): S10.
29.
Krawczyk M, Wang DQ, Portincasa P, et al. Dissecting the genetic heterogeneity of gallbladder stone formation. Semin Liver Dis. 2011; 31(2): 157–72.
30.
Uppal H, Zhai Y, Gangopadhyay A, et al. Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization. Hepatology. 2008; 47(4): 1331–1342.
31.
Jiang ZY, Parini P, Eggertsen G, et al. Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients. J Lipid Res. 2008; 49(2): 464–472.
32.
Biddinger S, Haas J, Yu B, et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med. 2008; 14(7): 778–782.
33.
van Mil SW, van der Woerd WL, van der Brugge G, et al. Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology. 2004; 127(2): 379–384.
34.
Poupon R, Arrive L, Rosmorduc O. The cholangiographic features of severe forms of ABCB4/MDR3 deficiency-associated cholangiopathy in adults. Gastroenterol Clin Biol. 2010; 34(6–7): 380–387.
35.
Acalovschi M, Tirziu S, Chiorean E, et al. Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs with gallstones, and controls. Lipids. 2009; 44(6): 521–526.
36.
Davit-Spraul A, Gonzales E, Baussan C, et al. The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects. Semin Liver Dis. 2010; 30(2): 134–146.
37.
Marschall HU, Katsika D, Rudling M, et al. The genetic background of gallstone formation: an update. Biochem Biophys Res Commun. 2010; 396(1): 58–62.
38.
Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med. 2004; 10(12): 1352–1358.
39.
Kovacs P, Kress R, Rocha J, et al. Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans. J Hepatol. 2008; 48(1): 116–24.
40.
Cui Y, Li Z, Zhao E, et al. Overexpression of Sterol Carrier Protein 2 in patients with hereditary cholesterol gallstones. BMC Gastroenterol. 2011; 11: 10.
41.
Seneshaw M, Marques DM, Pandak M, et al. Disruption of sterol carrier protein 2 (SCP2) and fatty acid binding protein 1 (FABP1) genes lowers the incidence of cholesterol gallstones. Gastroenterology. 2011; 140(5 SUPPL.1), s. S888.
42.
Chu CH, Yang AM, Kao JH, et al. Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism is associated with choledocholithiasis in Taiwanese patients. J Gastroenterol Hepatol. 2009; 24(9): 1559–1561.
43.
Brink MA, Slors JF, Keulemans YC, et al. Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn’s disease. Gastroenterology. 1999; 116(6): 1420–1427.
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