Abstract:
:Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype x environment (G x E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G x E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G x E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G x E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20-0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence.
journal_name
Addict Bioljournal_title
Addiction biologyauthors
Nelson EC,Agrawal A,Pergadia ML,Wang JC,Whitfield JB,Saccone FS,Kern J,Grant JD,Schrage AJ,Rice JP,Montgomery GW,Heath AC,Goate AM,Martin NG,Madden PAdoi
10.1111/j.1369-1600.2009.00181.xsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
1-11issue
1eissn
1355-6215issn
1369-1600pii
ADB181journal_volume
15pub_type
杂志文章abstract::Exposure to smoking-associated environmental cues during smoke cessation elicits self-reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue-induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue-...
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