Replication and extension of association of choline acetyltransferase with nicotine dependence in European and African American smokers

Abstract

Choline acetyltransferase is critical in the synthesis of acetylcholine and regulation of cholinergic neuron functions. We recently reported association of the encoding gene ChAT with both smoking cessation and nicotine dependence (ND) in two independent European American (EA) samples; however, in the replication sample, only limited SNPs partially covering the gene were examined. In this study, we examined the association of 14 SNPs, which cover the entire gene, with ND, assessed by smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström Test for ND (FTND), in 2,037 subjects from 602 families of African American (AA) or EA origin. Individual SNP-based association analysis revealed that Wve SNPs showed nominal association with at least one ND measure in one of the samples (P = 0.022-0.042); none remained signiWcant after correction for multiple testing. Haplotype-based association analysis revealed that haplotypes G-G-A-C, formed by rs1880676-rs3810950- rs10082479-rs8178990 (P = 0.005-0.0178), and G-G-T- C-G-C, formed by rs1880676-rs3810950-rs10082479- rs8178990-rs3793790-rs12266458 (P = 0.00247-0.00468), displayed signiWcant association with all three ND measures in the AA sample, as did haplotype T-C-G-A-T, formed by rs12266458-rs11101191-rs8178991-rs4838544- rs4838547 (P = 0.00741-0.0103), in the EA sample. All these detected haplotype-based associations remained signiWcant after correction for all major haplotypes for a given SNP combination. Together, our Wndings, in conjunction with the previous report of the association, warrant further investigation of ChAT in ND. © 2010 Springer-Verlag.