| Object:To dig up endophenotype of drug addition,reduce clinical heterogeneity and provide a new method to genetic research for the complex disease of drug addition;To evaluate the association between CREB (CREBl and ATF-2) andΔFosB genes with heroin-induced subjective responses, and offer a new perspective to the research for drug addition.Method:To evaluate the association of CREB andΔFosB variants with heroin-induced positive responses on first use, we studied 557 Chinese heroin addicts at convalescence recruited in Shanghai Mental Health Center and divided heroin addicts into three groups (positive, negative and even) according to the self-reporting feeling on first use. Association analyses with the genotypes and alleles in 10 tagging single nucleotide polymorphisms (tSNPs) of CREB1 and ATF-2,7 tSNPs ofΔFosB with subjective responses were performed. Similar analysis with haplotypes of these tSNPs was also performed.Results:Allele frequency of the tSNP rs 16839883 was significantly different between the positive and negative groups (p=.0013). Such association remained after adjustment for demographic covariates and for multiple testing. Specific haplotype GC of rs16839883 with rs2254137 showed significant association with drug addict (p=0.0097, OR=1.57,95%CI=1.06-2.34). rs2276470 (p=0.033)inΔFosB was associated with heroin-induced positive responses on first use; however, the association vanished after considering multiple tests(p=0.232).Conclusions:Self-reported positive responses on first use of heroin were found to be associated with single nucleotide polymorphysm of CREB1 gene,and there is no evidence to support the association with ATF-2 andΔFosB. |
