Details of Disease

General Information of Disease (ID: DISERLZB)

• Disease Name: Cholelithiasis
• Synonyms: GBD4; gallbladder disease 4; gallstones; gallbladder disease type 4
• Disease Class: DC11: Cholelithiasis
• Definition: The presence of calculi in the gallbladder.
• Disease Hierarchy:
  DISZJ4KB: Hereditary gallbladder disorder
  DISTVIQI: Bladder disease
  DISERLZB: Cholelithiasis
• ICD Code:
  ICD-11: ICD-11: DC11
  ICD-10: ICD-10: K80, K80.8
  Expand ICD-11: 'DC11
  Expand ICD-10: 'K80; 'K80.8
• Disease Identifiers:
  MONDO ID: MONDO_0012672
  MESH ID: D002769
  UMLS CUI: C0008350
  MedGen ID: 3039
  HPO ID: HP:0001081
  SNOMED CT ID: 266474003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Chenodiol	DMQ8JIK	Approved	Small molecular drug	[1]
Cholic Acid	DM7OKQV	Approved	Small molecular drug	[2]
Ursodeoxycholic acid	DMCUT21	Approved	Small molecular drug	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 22 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CCKAR	TTCG0AL	Limited	Altered Expression	[4]
HNF4A	TT2F3CD	Limited	Genetic Variation	[5]
MUC5AC	TTEL90S	Limited	Genetic Variation	[6]
PNPLA3	TTEUAEH	Limited	Genetic Variation	[7]
RNASEL	TT7V0K4	Limited	Genetic Variation	[8]
ABCB11	TTUXCAF	moderate	Altered Expression	[9]
HBA2	TTQO71U	moderate	Genetic Variation	[10]
SLC10A2	TTPI1M5	moderate	Genetic Variation	[5]
ABCG5	TTKZ7WY	Strong	Altered Expression	[9]
BAZ2B	TT6K8YG	Strong	Genetic Variation	[11]
CLIC1	TT8KZG6	Strong	Altered Expression	[12]
DPEP1	TTYUENF	Strong	Biomarker	[13]
FABP2	TTS4YLO	Strong	Genetic Variation	[14]
GLP2R	TT1YWO5	Strong	Genetic Variation	[15]
GUSB	TTHS7CM	Strong	Biomarker	[16]
LRP2	TTPH1AJ	Strong	Altered Expression	[17]
MAP2K5	TTV3O87	Strong	Genetic Variation	[18]
NPC1L1	TTPD1CN	Strong	Genetic Variation	[19]
SLC10A1	TTWZRY5	Strong	Biomarker	[20]
TNC	TTUCPMY	Strong	Genetic Variation	[11]
CCK	TT90CMU	Definitive	Biomarker	[21]
SLCO1A2	TTUGD21	Definitive	Biomarker	[22]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC22A7	DT0OC1Q	Strong	Genetic Variation	[23]
SLC51B	DT1V9AJ	Strong	Altered Expression	[24]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP7A1	DEDZRQ1	Strong	Genetic Variation	[25]
CYP8B1	DETL4WB	Strong	Genetic Variation	[26]
FMO3	DEP76YL	Strong	Biomarker	[27]

This Disease Is Related to 32 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PLA2G10	OTRZ2L5A	Limited	Biomarker	[28]
ACAT2	OTZ092ZJ	Strong	Altered Expression	[29]
APOBEC1	OTY8QX2R	Strong	Biomarker	[30]
APOC1	OTA58CED	Strong	Genetic Variation	[31]
ASPG	OT5E2EKR	Strong	Biomarker	[32]
ATP11A	OT7M9ZDK	Strong	Altered Expression	[33]
BMF	OT90NSLI	Strong	Altered Expression	[34]
CA10	OTC3N1F6	Strong	Genetic Variation	[11]
CCL28	OTY6XNQ7	Strong	Biomarker	[35]
CDHR5	OTTBWQMN	Strong	Genetic Variation	[36]
CHD1L	OT7CZK7C	Strong	Altered Expression	[37]
DACH1	OTMKNAGG	Strong	Genetic Variation	[11]
FABP6	OTIRQWLW	Strong	Biomarker	[38]
FAIM2	OT6QINVO	Strong	Genetic Variation	[18]
FRMD4A	OTJDTIK2	Strong	Genetic Variation	[11]
GGTLC1	OTWJKUHQ	Strong	Biomarker	[39]
GNA14	OTYZ1ZI0	Strong	Genetic Variation	[11]
HHEX	OTLIUVYX	Strong	Genetic Variation	[18]
HMCN1	OTLZAS0P	Strong	Genetic Variation	[11]
L3MBTL4	OTERBGKR	Strong	Genetic Variation	[11]
LIX1	OT1CPNCC	Strong	Biomarker	[40]
MBNL1	OTOV7J85	Strong	Biomarker	[41]
MYO10	OTHB78ZQ	Strong	Genetic Variation	[11]
MYPN	OTHTOFDU	Strong	Genetic Variation	[11]
NRXN3	OTJ0I7HJ	Strong	Genetic Variation	[18]
OPN1MW	OTPJ7LX4	Strong	Genetic Variation	[42]
RPL4	OTTYJB0X	Strong	Genetic Variation	[43]
SGCZ	OTVGTEOD	Strong	Genetic Variation	[11]
SH2D4B	OTM0KLPH	Strong	Genetic Variation	[11]
STX12	OT5IBQ62	Strong	Genetic Variation	[11]
TANC1	OTF6TZ8E	Strong	Genetic Variation	[11]
TMEM114	OTLVG8X3	Strong	Genetic Variation	[11]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Cholic acid FDA Label
• [3] Management of symptomatic cholelithiasis: a systematic review. Syst Rev. 2022 Dec 12;11(1):267.
• [4] Polymorphism and Expression Profile of Cholecystokinin Type A Receptor in Relation to Gallstone Disease Susceptibility.Biochem Genet. 2016 Oct;54(5):665-75. doi: 10.1007/s10528-016-9745-x. Epub 2016 Jun 10.
• [5] Identification and Replication of Six Loci Associated With Gallstone Disease.Hepatology. 2019 Aug;70(2):597-609. doi: 10.1002/hep.30313. Epub 2019 Mar 4.
• [6] Gallstone Etiopathogenesis, Lith and Mucin Genes and New Treatment Approaches.Asian Pac J Cancer Prev. 2016;17(2):467-71. doi: 10.7314/apjcp.2016.17.2.467.
• [7] Genetics of gallstone disease revisited: updated inventory of human lithogenic genes.Curr Opin Gastroenterol. 2019 Mar;35(2):82-87. doi: 10.1097/MOG.0000000000000511.
• [8] Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.Cancer Res. 2008 Aug 1;68(15):6442-52. doi: 10.1158/0008-5472.CAN-08-0444.
• [9] Altered Bile Transporter Expression and Cholesterol Metabolism in Children With Cholesterol and Pigment Gallstones.J Pediatr Gastroenterol Nutr. 2019 Aug;69(2):138-144. doi: 10.1097/MPG.0000000000002353.
• [10] UGT1A1 (TA)(n) genotype is not the major risk factor of cholelithiasis in sickle cell disease children.Eur J Haematol. 2017 Mar;98(3):296-301. doi: 10.1111/ejh.12838. Epub 2017 Jan 9.
• [11] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [12] CLIC1 overexpression is associated with poor prognosis in gallbladder cancer.Tumour Biol. 2015 Jan;36(1):193-8. doi: 10.1007/s13277-014-2606-5. Epub 2014 Sep 17.
• [13] Intense 99mTc-MDP Activity in an Elongated Sagging Gallbladder With a Partially Calcified Gallstone.Clin Nucl Med. 2017 Sep;42(9):733-734. doi: 10.1097/RLU.0000000000001759.
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• [15] New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.J Clin Endocrinol Metab. 2019 Jul 1;104(7):2463-2472. doi: 10.1210/jc.2018-01008.
• [16] Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria.Sci Rep. 2015 Dec 2;5:17450. doi: 10.1038/srep17450.
• [17] Participation of the SMAD2/3 signalling pathway in the down regulation of megalin/LRP2 by transforming growth factor beta (TGF-1).PLoS One. 2019 May 23;14(5):e0213127. doi: 10.1371/journal.pone.0213127. eCollection 2019.
• [18] Metabolic biomarkers and gallstone disease - a population-based study.Scand J Gastroenterol. 2017 Nov;52(11):1270-1277. doi: 10.1080/00365521.2017.1365166. Epub 2017 Aug 11.
• [19] Genetic polymorphism of sterol transporters in children with future gallstones.Dig Liver Dis. 2018 Sep;50(9):954-960. doi: 10.1016/j.dld.2018.04.007. Epub 2018 Apr 26.
• [20] Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients.Medicine (Baltimore). 2019 Sep;98(39):e17305. doi: 10.1097/MD.0000000000017305.
• [21] Impaired intestinal cholecystokinin secretion, a fascinating but overlooked link between coeliac disease and cholesterol gallstone disease.Eur J Clin Invest. 2017 Apr;47(4):328-333. doi: 10.1111/eci.12734. Epub 2017 Mar 8.
• [22] Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1.Hematology. 2016 Mar;21(2):121-5. doi: 10.1179/1607845415Y.0000000030. Epub 2015 Jul 6.
• [23] Organic anion transporter protein (OATP1B1) encoded by SLCO1B1 gene polymorphism (388A>G) & susceptibility in gallstone disease.Indian J Med Res. 2009 Feb;129(2):170-5.
• [24] Reduced ileal expression of OSTalpha-OSTbeta in non-obese gallstone disease.J Lipid Res. 2008 Sep;49(9):2045-54. doi: 10.1194/jlr.M800162-JLR200. Epub 2008 May 9.
• [25] Genetic variants in CYP7A1 and risk of myocardial infarction and symptomatic gallstone disease.Eur Heart J. 2018 Jun 7;39(22):2106-2116. doi: 10.1093/eurheartj/ehy068.
• [26] Single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese.J Gastroenterol Hepatol. 2013 Apr;28(4):717-22. doi: 10.1111/jgh.12089.
• [27] FMO3 and its metabolite TMAO contribute to the formation of gallstones.Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2576-2585. doi: 10.1016/j.bbadis.2019.06.016. Epub 2019 Jun 26.
• [28] Secretory low-molecular-weight phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholangitis.Hepatology. 1999 Apr;29(4):1026-36. doi: 10.1002/hep.510290440.
• [29] Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients.Biochem Biophys Res Commun. 2009 Jan 30;379(1):49-54. doi: 10.1016/j.bbrc.2008.11.131. Epub 2008 Dec 9.
• [30] Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease.Liver Int. 2007 Sep;27(7):910-9. doi: 10.1111/j.1478-3231.2007.01536.x.
• [31] Association of APOE-C1 gene cluster polymorphisms with gallstone disease.Dig Liver Dis. 2006 Jun;38(6):397-403. doi: 10.1016/j.dld.2006.02.005. Epub 2006 May 2.
• [32] Cholelithiasis and choledocholithiasis after sequential cytarabine and asparaginase.J Pediatr Hematol Oncol. 2003 Aug;25(8):637-9. doi: 10.1097/00043426-200308000-00010.
• [33] An integrated analysis of differential miRNA and mRNA expressions in human gallstones.Mol Biosyst. 2015 Apr;11(4):1004-11. doi: 10.1039/c4mb00741g.
• [34] Gene expression profiling reveals upregulated UCA1 and BMF in gallbladder epithelia of children with pancreaticobiliary maljunction.J Pediatr Gastroenterol Nutr. 2011 Jun;52(6):744-50. doi: 10.1097/MPG.0b013e318214bd30.
• [35] Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones.Curr Med Chem. 2019;26(19):3407-3423. doi: 10.2174/0929867324666170619104801.
• [36] Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease.Clin Chim Acta. 2011 Nov 20;412(23-24):2089-93. doi: 10.1016/j.cca.2011.07.015. Epub 2011 Aug 1.
• [37] Clinical significance of chromodomain helicase/ATPase DNA binding protein 1-like and human mutL homolog 1 gene expression in cholangiocarcinoma.Oncol Lett. 2018 Sep;16(3):2989-2994. doi: 10.3892/ol.2018.9043. Epub 2018 Jun 28.
• [38] Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers.J Lipid Res. 2006 Jan;47(1):42-50. doi: 10.1194/jlr.M500215-JLR200. Epub 2005 Oct 19.
• [39] Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy.Hepatology. 2007 Jan;45(1):150-8. doi: 10.1002/hep.21500.
• [40] Single hospital visit elective day-case laparoscopic cholecystectomy without prior outpatient attendance.Surg Endosc. 2017 Sep;31(9):3574-3580. doi: 10.1007/s00464-016-5387-7. Epub 2017 Jan 26.
• [41] A putative role of ribonuclear inclusions and MBNL1 in the impairment of gallbladder smooth muscle contractility with cholelithiasis in myotonic dystrophy type 1.Neuromuscul Disord. 2008 Aug;18(8):641-5. doi: 10.1016/j.nmd.2008.06.366. Epub 2008 Jul 23.
• [42] Laparo-endoscopic rendez-vous versus sequential "delayed" approach in patients with choledocholithiasis.Minerva Chir. 2017 Apr;72(2):98-102. doi: 10.23736/S0026-4733.16.07248-5. Epub 2016 Dec 16.
• [43] Antibiotic activity of antimicrobial peptide against Pseudomonads isolated from a patient with gallstones.Protein Pept Lett. 2006;13(1):53-8. doi: 10.2174/092986606774502018.