Details of Disease

General Information of Disease (ID: DIS7INCX)

• Disease Name: Alcohol withdrawal
• Synonyms: alcohol withdrawal syndrome
• Disease Hierarchy:
  DISTT24U: Substance withdrawal syndrome
  DIS7INCX: Alcohol withdrawal
• Disease Identifiers:
  MONDO ID: MONDO_0005433
  UMLS CUI: C0236663
  MedGen ID: 536543
  SNOMED CT ID: 191480000

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
Chlordiazepoxide	DMTN5XI	Approved	Small molecular drug	[1]
Clorazepate	DMC3JST	Approved	Small molecular drug	[2]
Diazepam	DM08E9O	Approved	Small molecular drug	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AR	TTKPW01	Limited	Biomarker	[4]
DBH	TTYIP79	Limited	Genetic Variation	[5]
FKBP5	TT0J5KQ	Limited	Biomarker	[6]
GLUL	TTURQ2G	Limited	Biomarker	[7]
GRIN1	TTLD29N	Limited	Altered Expression	[8]
GRIN2B	TTN9D8E	Limited	Genetic Variation	[9]
KCNQ4	TT8HGRW	Limited	Biomarker	[10]
TMEM97	TT9NXW4	Limited	Biomarker	[11]
CFP	TTLA0VS	moderate	Biomarker	[12]
HTR2C	TTWJBZ5	moderate	Biomarker	[13]
NPY1R	TTRK9JT	moderate	Biomarker	[14]
NPY2R	TTJ6WK9	moderate	Biomarker	[14]
NPY5R	TTY6EWA	moderate	Biomarker	[14]
NQO2	TTJLP0R	moderate	Biomarker	[15]
CYP19A1	TTSZLWK	Strong	Biomarker	[4]
KDM4C	TTV8CRH	Strong	Genetic Variation	[16]
LEP	TTBJEZ5	Strong	Posttranslational Modification	[17]
NGF	TTDN3LF	Strong	Biomarker	[18]
SLC6A3	TTVBI8W	Strong	Posttranslational Modification	[19]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC18A1	DTM953D	Limited	Genetic Variation	[20]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
C1D	OTI9PMN1	moderate	Genetic Variation	[21]
PNOC	OTJEAADN	moderate	Biomarker	[22]
MPDZ	OT9WY1QM	Strong	Biomarker	[23]
SORCS2	OTBF3DYK	Strong	Biomarker	[24]

References

• [1] Chlordiazepoxide FDA Label
• [2] Clorazepate FDA Label
• [3] Diazepam FDA Label
• [4] The TTTAn aromatase (CYP19A1) polymorphism is associated with compulsive craving of male patients during alcohol withdrawal.Psychoneuroendocrinology. 2011 Sep;36(8):1261-4. doi: 10.1016/j.psyneuen.2011.02.010. Epub 2011 Mar 16.
• [5] DBH*444G/A polymorphism of the dopamine-beta-hydroxylase gene is associated with alcoholism but not with severe alcohol withdrawal symptoms.J Neural Transm (Vienna). 2006 Jul;113(7):869-76. doi: 10.1007/s00702-005-0365-6. Epub 2005 Oct 27.
• [6] The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans.Int J Mol Sci. 2016 Aug 5;17(8):1271. doi: 10.3390/ijms17081271.
• [7] Glutamate decarboxylase genes and alcoholism in Han Taiwanese men.Alcohol Clin Exp Res. 2006 Nov;30(11):1817-23. doi: 10.1111/j.1530-0277.2006.00218.x.
• [8] Memantine attenuated alcohol withdrawal-induced anxiety-like behaviors through down-regulating NR1-CaMKII-ERK signaling pathway.Neurosci Lett. 2018 Nov 1;686:133-139. doi: 10.1016/j.neulet.2018.09.006. Epub 2018 Sep 10.
• [9] Association of N-Methyl-D-Aspartate receptor 2B Subunit (GRIN2B) polymorphism with earlier age at onset of withdrawal symptoms in Indian alcohol dependent subjects.J Addict Dis. 2017 Jan-Mar;36(1):48-52. doi: 10.1080/10550887.2016.1140434. Epub 2016 Jan 15.
• [10] Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents.Neuropharmacology. 2018 Aug;138:10-19. doi: 10.1016/j.neuropharm.2018.05.020. Epub 2018 May 25.
• [11] Small molecule modulators of 2R/Tmem97 reduce alcohol withdrawal-induced behaviors.Neuropsychopharmacology. 2018 Aug;43(9):1867-1875. doi: 10.1038/s41386-018-0067-z. Epub 2018 Apr 20.
• [12] Elevated monoamine oxidase A activity and protein levels in rodent brain during acute withdrawal after chronic intermittent ethanol vapor exposure.Drug Alcohol Depend. 2018 Apr 1;185:398-405. doi: 10.1016/j.drugalcdep.2017.11.036. Epub 2018 Feb 5.
• [13] Anxiety during alcohol withdrawal involves 5-HT2C receptors and M-channels in the lateral habenula.Neuropharmacology. 2020 Feb;163:107863. doi: 10.1016/j.neuropharm.2019.107863. Epub 2019 Nov 26.
• [14] Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence.Alcohol Clin Exp Res. 2008 Dec;32(12):2031-40. doi: 10.1111/j.1530-0277.2008.00790.x. Epub 2008 Sep 25.
• [15] Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms.Alcohol Clin Exp Res. 2003 Aug;27(8 Suppl):68S-71S. doi: 10.1097/01.ALC.0000078616.63296.41.
• [16] Genome-wide association study identifies 5q21 and 9p24.1 (KDM4C) loci associated with alcohol withdrawal symptoms.J Neural Transm (Vienna). 2012 Apr;119(4):425-33. doi: 10.1007/s00702-011-0729-z. Epub 2011 Nov 11.
• [17] DNA Methylation of the Leptin Gene Promoter is Altered by Chronic Alcohol Exposure in an Animal Model for Alcohol Dependence.Eur Addict Res. 2019;25(2):49-55. doi: 10.1159/000496111. Epub 2019 Jan 16.
• [18] Epigenetic down regulation of nerve growth factor during alcohol withdrawal.Addict Biol. 2013 May;18(3):508-10. doi: 10.1111/j.1369-1600.2010.00307.x. Epub 2011 Mar 11.
• [19] Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving.J Psychiatr Res. 2009 Jan;43(4):388-92. doi: 10.1016/j.jpsychires.2008.04.006. Epub 2008 May 27.
• [20] Genetic Variation in the Vesicular Monoamine Transporter 1 (VMAT1/SLC18A1) Gene and Alcohol Withdrawal Severity.Alcohol Clin Exp Res. 2016 Mar;40(3):474-81. doi: 10.1111/acer.12991. Epub 2016 Feb 15.
• [21] Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.Pharmacol Rep. 2012;64(5):1126-34. doi: 10.1016/s1734-1140(12)70909-x.
• [22] Nociceptin Receptors Upregulated in Cocaine Use Disorder: A Positron Emission Tomography Imaging Study Using [(11)C]NOP-1A.Am J Psychiatry. 2019 Jun 1;176(6):468-476. doi: 10.1176/appi.ajp.2019.18081007. Epub 2019 May 6.
• [23] Mpdz expression in the caudolateral substantia nigra pars reticulata is crucially involved in alcohol withdrawal.Genes Brain Behav. 2014 Nov;13(8):769-76. doi: 10.1111/gbb.12171. Epub 2014 Sep 17.
• [24] Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2.Front Pharmacol. 2019 May 17;10:499. doi: 10.3389/fphar.2019.00499. eCollection 2019.