Association study of the Epac gene and tobacco smoking and nicotine dependence.
Exchange protein directly activated by cAMP (Epac) has been shown to increase its expression in rat prefrontal cortex after self-administration of nicotine. [Konu et al. 2001: Brain Res 909:194-203]. We investigated the role of the human ortholog of Epac in tobacco smoking and nicotine dependence (ND). Using a case-control design, we typed 5 SNPs in this gene in 688 subjects, of whom 244 were non-smokers, 215 were Low-ND smokers, and 229 were High-ND smokers. We tested allele and genotype association to smoking initiation (SI) and progression to ND. Three of the five typed SNPs showed modest allele association with progression to ND. Weak association with SI was also observed for one SNP. Considering the function of the gene in cellular signal transduction pathway, its elevated expression after nicotine self-administration, and multiple markers association with both SI and progression to ND, it is plausible to suggest that variants in Epac contribute to the liability to ND.
Virginia Institute for Psychiatric and Behavior Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia 23298, USA. xchen@vcu.edu
Xiangning
X
Chen
Baichai
B
Wu
Kenneth S
KS
Kendler
D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human