Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.
- Authors
- Zhu, A Z X; Zhou, Q; Cox, L S; David, S P; Ahluwalia, J S; Benowitz, N L; Tyndale, R F
- Year
- 2014
- Journal
- Clinical pharmacology and therapeutics
- PMID
- 24733007
- DOI
- 10.1038/clpt.2014.88
- PMCID
- PMC4111775
Associations between CHRNA5-A3-B4 variants and smoking behaviors exist; however, the association with smoking abstinence is less understood, particularly that among African Americans. In 1,295 African Americans enrolled in two clinical trials, we investigated the association between CHRNA5-A3-B4 and smoking abstinence. The rs2056527(A) allele was associated with lower abstinence with active pharmacotherapy (during treatment: odds ratio (OR) = 0.42, P < 0.001; end of treatment (EOT): OR = 0.55, P = 0.004), or with nicotine gum alone (during treatment: OR = 0.31, P < 0.001; EOT: OR = 0.51, P = 0.02), but not significantly with bupropion, although similar directions and magnitudes were observed (during treatment: OR = 0.54, P = 0.05; EOT: OR = 0.59, P = 0.08). In addition, the rs588765(T) allele was associated with abstinence with gum during treatment (OR = 2.31, P < 0.01). The SNP rs16969968 occurred at a low frequency and was not consistently associated with abstinence. CHRNA5-A3-B4 variants were not associated with tobacco consumption, and adjustments for smoking behaviors did not alter the associations with smoking abstinence. Together, our data suggest that among African Americans, CHRNA5-A3-B4 variants are not associated with baseline smoking but can influence smoking abstinence during active pharmacotherapy.
The associations (dominant model) between CHRNA5-A3-B5 variants and smoking abstinence in African American smokers. A) Participants who received active nicotine gum treatment (Study 1). B) Participants who received active bupropion treatment (Study 2). C) Participants who received active pharmacological treatments (combined analysis). D) Participants who received placebo (combined analysis). P-values below 0.0125 were considered statistically significant due to multiple comparison adjustments. Statistically significant values are bolded.
The ‘A’ allele of rs2036527 was associated with lower smoking cessation rates in African American smokers receiving active pharmacological treatment. A) Participants in who received nicotine gum or placebo (Study 1). B) Participants who received active bupropion or placebo (Study 2). C) Participants who received active pharmacological treatments (combined analysis). ORunadj. = unadjusted odds ratio of quitting for the GA&AA genotype group compared to the GG genotype. ORadj.= odds ratio of quitting for the GA&AA genotype group compared to the GG genotype after adjusting for age, sex, baseline CPD, menthol status and type of counseling session. There was also a significant treatment (combined active vs. combined placebo) by rs2036527 genotype interaction during treatment (OR=0.43, P=0.01). The OR and P-values are shown for all comparisons with ORs smaller than 0.7 or greater than 1.4. P-values below 0.0125 were considered statistically significant due to multiple comparison adjustments. Statistically significant values are bolded. N represents the number of participants.
The ‘T’ allele of rs588765 was associated with smoking abstinence in African American smokers receiving active pharmacological treatment. A) Participants in who received nicotine gum or placebo (Study 1). B) Participants who received active bupropion or placebo (Study 2). C) Participants who received active pharmacological treatments (combined analysis). ORunadj. = unadjusted odds ratio of quitting for the CT&TT genotype group compared to the CC genotype. ORadj.= odds ratio of quitting for the CT&TT genotype group compared to the CC genotype after adjusting for age, sex, baseline CPD, menthol status and type of counseling sessions. There was also a significant treatment (combined active vs. combined placebo) by rs588765 genotype interaction during treatment (OR=3.75, P<0.001). The OR and P-values are shown for all comparisons with ORs smaller than 0.7 or greater than 1.4. P-values below 0.0125 were considered statistically significant due to multiple comparison adjustments. Statistically significant values are bolded. N represents the number of participants.
Rs16969968 was not consistently associated with smoking abstinence in African American smokers receiving active pharmacological treatment. A) Participants in who received nicotine gum or placebo (Study 1). B) Participants who received active bupropion or placebo (Study 2). C) Participants who received active pharmacological treatments (combined analysis). ORunadj. = unadjusted odds ratio of quitting for the GA&AA genotype group compared to the GG genotype. ORadj.= odds ratio of quitting for the GA&AA genotype group compared to the GG genotype after adjusting for age, sex, baseline CPD, menthol status and type of counseling sessions. The OR and P-values are shown for all comparisons with ORs smaller than 0.7 or greater than 1.4. P-values below 0.0125 were considered statistically significant due to multiple comparison adjustments. Statistically significant values are bolded. N represents the number of participants.
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