Why do young women smoke? V. Role of direct and interactive effects of nicotinic cholinergic receptor gene variation on neurocognitive function.

Previous work suggests that young women who smoke cigarettes regularly, or did so in the past, manifest a neurocognitive profile that is characterized by small but significant impairments of response inhibition and attention. The present study sought to determine whether variation in nicotinic cholinergic receptor (nAchR) genes impacts upon cognitive function in these domains by overall or differential effects on the performance of current, former and non-smokers. The study sample consisted of 100 female college students, current or past smokers, and 144 who had never smoked. All performed a computerized neurocognitive test battery and were genotyped for 39 single nucleotide polymorphisms in 11 nAchR genes. The results, derived from linear or logistic regression, show significant direct and interactive relationships between single nucleotide polymorphisms and haplotypes in several nAchR genes and performance on the Matching Familiar Figures Test (MFFT) Stroop test, Continuous Performance Task (CPT) and Tower of London (TOL) test. Response inhibition (MFFT, Stroop, CPT Loading Phase, TOL) was associated with variants in CHRNA2, CHRNA4, CHRNA5, CHRNA7, CHRNA9, CHRNA10, CHRNB2 and CHRNB3. Selective attention (Stroop) was associated with CHRNA4, CHRNA5, CHRNA9 and CHRNB2. Sustained attention (CPT Boring Phase) was associated with CHRNA4, CHRNA5, CHRNA7, CHRNA10 and CHRNB3. Up to 37% of the variance among the smokers and up to 47% of the variance among the non-smokers on the test measures was explained. Differences between smokers and non-smokers in neurocognitive function, putatively implicated in susceptibility to nicotine dependence, may be modulated by variants in nAchR genes, with potential implications for prevention and treatment.