Details

Autor(en) / Beteiligte

• Li, Ming D
• Beuten, Joke
• Ma, Jennie Z
• Payne, Thomas J
• Lou, Xiang-Yang
• Garcia, Veronica
• Duenes, Aristeo S
• Crews, Karen M
• Elston, Robert C

Titel

Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4) with nicotine dependence

Ist Teil von

• Human molecular genetics, 2005-05, Vol.14 (9), p.1211-1219

Erscheinungsjahr

2005

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• We tested six single nucleotide polymorphisms (SNPs) in the alpha 4 subunit gene (CHRNA4) and four SNPs in the beta 2 subunit gene (CHRNB2) of nicotinic acetylcholine receptors (nAChRs) for association with nicotine dependence (ND), which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstroem test for ND (FTND) in 2037 subjects from 602 nuclear families of either European-American (EA) or African-American (AA) ancestry. Analysis of the six SNPs within CHRNA4 demonstrated that in the EA sample SNPs rs2273504 and rs1044396 are significantly associated with the adjusted SQ and FTND score, respectively. In the AA samples, SNPs rs3787137 and rs2236196 are each significantly associated with at least two adjusted ND measures. Association of rs2236196 with the adjusted HSI and FTND scores in the AA samples remained significant after correction for multiple testing. Furthermore, analysis revealed gender- and ethnic-specific associations for several SNPs with ND measures in both ethnic samples; however, only the association of SNP rs2236196 with the three adjusted ND measures remained significant after correcting for multiple testing in the AA female samples. Haplotype analysis of rs2273505-rs2273504-rs2236196 showed significant association after Bonferroni correction of a C-G-G haplotype (53.4%) with three adjusted ND measures in samples from the AA females. A similar analysis for the four SNPs within CHRNB2 did not reveal significant association with the three ND measures. In summary, our findings provide convincing evidence for the involvement of the nAChR alpha 4 subunit, but not of the nAChR beta 2 subunit, in nicotine addiction.