Document Detail


ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.
MedLine Citation:
PMID:  23303482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging.
OBJECTIVE: To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations.
DESIGN: Case-control genetic association study that included 2 control groups (lacking an established optimal control group).
SETTING: Semistructured psychiatric interviews.
PARTICIPANTS: A total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample.
MAIN OUTCOME MEASURE: Lifetime heroin dependence.
RESULTS: Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P ≥ .01); a similar comparison with neighborhood controls revealed greater differences (P ≥ 1.8 × 10(-4)). Comparing cases (n = 1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n = 340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio = 1.59; 95% CI, 1.32-1.92; P = 9.7 × 10(-7)), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n = 191) and nondependent (n = 340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P = 2.7 × 10(-9) for the risk-associated linear trend).
CONCLUSIONS: Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.
Authors:
Elliot C Nelson; Michael T Lynskey; Andrew C Heath; Naomi Wray; Arpana Agrawal; Fiona L Shand; Anjali K Henders; Leanne Wallace; Alexandre A Todorov; Andrew J Schrage; Nancy L Saccone; Pamela A F Madden; Louisa Degenhardt; Nicholas G Martin; Grant W Montgomery
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-05-02     Revised Date:  2014-11-12    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  325-33     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD56 / genetics*
Australia
Case-Control Studies
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Heroin Dependence / genetics*
Humans
Logistic Models
Male
Middle Aged
Polymorphism, Single Nucleotide
Protein-Serine-Threonine Kinases / genetics*
Proteins / genetics*
Receptors, Dopamine D2 / genetics
Grant Support
ID/Acronym/Agency:
K05 AA017688/AA/NIAAA NIH HHS; R01 DA017305/DA/NIDA NIH HHS; R01 DA017305/DA/NIDA NIH HHS; R01 DA023668/DA/NIDA NIH HHS; R01 DA23668/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD56; 0/NCAM1 protein, human; 0/Proteins; 0/Receptors, Dopamine D2; 0/TTC12 protein, human; EC 2.7.11.1/ANKK1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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