RGD Reference Report - Multiple polymorphisms in genes of the adrenergic stress system confer vulnerability to alcohol abuse. - Rat Genome Database

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Multiple polymorphisms in genes of the adrenergic stress system confer vulnerability to alcohol abuse.

Authors: Clarke, Toni-Kim  Dempster, Emma  Docherty, Sophia J  Desrivieres, Sylvane  Lourdsamy, Anbarasu  Wodarz, Norbert  Ridinger, Moniker  Maier, Wolfgang  Rietschel, Marcella  Schumann, Gunter 
Citation: Clarke TK, etal., Addict Biol. 2012 Jan;17(1):202-8. doi: 10.1111/j.1369-1600.2010.00263.x. Epub 2010 Nov 11.
RGD ID: 401976462
Pubmed: PMID:21070505   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1369-1600.2010.00263.x   (Journal Full-text)

Environmental factors such as stress influence both the predisposition to and development of alcoholism, as well as have significant implications for alcoholism relapse. One predominant biological response to acute stress is the release of norepinephrine, which activates the peripheral stress response and also the hypothalamic-pituitary-adrenal axis. We aimed to examine the role of two genes of the adrenergic system (SLC6A2 and ADRA2A) in alcoholism by genotyping 21 SNPs in 785 adult alcohol-dependent patients and 1237 controls. Two single nucleotide polymorphisms (SNP) (rs36020 and rs36029) in SLC6A2 were significantly associated with alcoholism [false discovery rate corrected P-value (FDR) P = 0.007]. Two SNPs in ADRA2A (rs521674 and rs602618) were associated with a positive family history of alcoholism (FDR P <= 0.05). A combined SNP-set analysis was also carried out to determine the risk of harbouring multiple alcohol risk alleles across SLC6A2 and ADRA2A. Logistic regression analysis revealed that an increase in the number of alcohol risk alleles increased the risk for alcoholism (P = 0.000567, odds ratio = 1.75, 95% confidence interval 1.26-2.44). A three-SNP haplotype consisting of rs187715, rs36020 and rs40147 alleles, AGC, was also found, which was significantly over-represented in cases compared with controls (61% versus 56%). We therefore demonstrate an association of SLC6A2 and ADRA2A with adult alcoholism. These data confirm the relevance of the adrenergic stress system when considering genetic predisposition to alcohol dependence and suggest that SLC6A2 and ADRA2A should be studied in additional alcohol-dependent cohorts.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADRA2AHumanalcohol dependence susceptibilityIAGP DNA:SNP:promoter: C-1291G (rs1800544) (human)RGD 
Adra2aRatalcohol dependence susceptibilityISOADRA2A (Homo sapiens)DNA:SNP:promoter: C-1291G (rs1800544) (human)RGD 
Adra2aMousealcohol dependence susceptibilityISOADRA2A (Homo sapiens)DNA:SNP:promoter: C-1291G (rs1800544) (human)RGD 
SLC6A2Humanalcohol dependence susceptibilityIAGP DNA:SNPs more ...RGD 
Slc6a2Ratalcohol dependence susceptibilityISOSLC6A2 (Homo sapiens)DNA:SNPs more ...RGD 
Slc6a2Mousealcohol dependence susceptibilityISOSLC6A2 (Homo sapiens)DNA:SNPs more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADRA2AHumanAddictive alcohol use susceptibilityIAGP DNA:SNP:promoter: C-1291G (rs1800544) (human)RGD 
SLC6A2HumanAddictive alcohol use susceptibilityIAGP DNA:SNPs more ...RGD 
ADRA2AHumanFamily history susceptibilityIAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Adra2a  (adrenoceptor alpha 2A)
Slc6a2  (solute carrier family 6 member 2)

Genes (Mus musculus)
Adra2a  (adrenergic receptor, alpha 2a)
Slc6a2  (solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2)

Genes (Homo sapiens)
ADRA2A  (adrenoceptor alpha 2A)
SLC6A2  (solute carrier family 6 member 2)


Additional Information