Association study of 45 candidate genes in nicotine dependence in Han Chinese.

Numerous genetic linkages, association studies have been performed in different ethnic groups and revealed many susceptibility loci and genes for nicotine dependence. However, limited similar researches were performed in Han Chinese. This study was designed to investigate the association of candidate genes with nicotine dependence in Han Chinese. We genotyped 384 SNPs within 45 candidate genes with nicotine dependence in a Han Chinese population consisting 223 high nicotine dependent subjects and 257 low nicotine dependent subjects by employing GoldenGate genotyping assay (Illumina). Following association analysis was performed using PLINK software. Individual SNP-based association analysis revealed that nine SNPs located in DRD3 (rs2630351), DRD5 (rs1967550), MAP3K4 (rs2314378), DDC (rs11575461), CHRNB3 (rs4954), GABBR2 (rs2779562), DRD2 (rs11214613 and rs6589377) and CHRNA4 (rs2236196) were significantly associated with FTND after correction for multiple testing with the p values from 2.59×10(-7) to 9.99×10(-5). Haplotype-based association analysis revealed haplotype G-A-A formed by rs2630351, rs167771 and rs324032 and haplotype G-G-G-A formed by rs3773678, rs2630349, rs2630351 and rs167771 in DRD3; haplotype of G-A formed by rs2779562 and rs2808566 in GABBR2 and haplotype of T-T-A-G-A formed by rs6832644, rs4057797, rs9764, rs4552421 and rs10033119 in NPY1R are associated with FTND (p=3.61×10(-7)-8.78×10(-6)). Our results provided confirmation of the previous findings that DRD2, DRD3, DDC, CHRNB3, GABBR2 and CHRNA4 are associated with nicotine dependence. Furthermore, we for the first time report a significant association between nicotine dependence and DRD5, MAP3K4 and NPY1R. These findings need independent replication in the future studies.