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Chunk #17 — Discussion — CHRNA5-A3-B4 and smoking abstinence

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Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.
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In Caucasians, a number of studies have examined the association between CHRNA5-A3-B4 gene variants and clinical trial outcomes for quitting smoking. These studies have varied in whether the predominant effect of CHRNA5-A3-B4 gene variants was in the placebo arm, a specific treatment arm, or in all active treatment arms more generally (15, 17, 20). Our observations regarding rs2036527 and smoking abstinence in African American smokers are in agreement with a previous report by Munafò and colleagues in Caucasians with rs1051730 (15). Both studies reported significant associations between CHRNA5-A3-B4 gene variants and abstinence 1) primarily in the active pharmacological therapy groups, with little effect observable within the placebo arm, and 2) only during treatment (no association remains at follow up, after active treatment had stopped). Of note, in Caucasians rs2036527 is in high linkage disequilibrium with rs1051730 (r2=0.90). Therefore, rs2036527 may be a better pharmacogenetic marker for smoking cessation than rs16969968/rs1051730 as it predicts similar relapse risks in both Caucasians and African Americans.