Single Nucleotide Polymorphisms in CHRNA5 rs16969968, CHRNA3 rs578776, and LOC123688 rs8034191 Are Associated With Heaviness of Smoking in Women in Northeastern Ontario, Canada

Introduction: The development of nicotine dependence (ND) is an important final step in the development of nicotine addiction, is associated with substantial morbidity and mortality, and makes long-term smoking cessation difficult. Methods: We used questionnaire data and DNA from buccal swabs previously collected from a population-based case-control study in Northeastern Ontario, Canada; an area with high smoking and smoking-related disease rates. Women smokers were classified into heavy and light phenotypes, a proxy for ND, and we assessed the association between phenotype and single nucleotide polymorphisms (SNPs) that have been associated with increased or decreased risk of ND. Results: Women with the variant AA genotype of CHRNA5 rs16969968 or variant CC genotype of LOC123688 rs8034191 were at significantly increased risk of heavy smoking, with age-adjusted odds ratios (ORs) of 3.2 (95% CI: 1.05-10.0) and 2.8 (95% CI: 1.00-7.91), respectively. Women with the variant AA genotype of CHRNA3 rs578775 were at significantly decreased risk of heavy smoking, with an age-adjusted OR of 0.3 (95% CI: 0.12-0.90). Conclusion: SNPs from 2 distinct variant groups were significantly associated with heaviness of smoking in this homogeneous population of women with high smoking rates, and this study supports the interpretation that there are different mechanisms of nicotine addiction involving both increasing and decreasing risk.