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Chunk #29 — Discussion

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Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene cluster with nicotine dependence in African and European Americans.
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Although the association of the CHRNA5/A3/B4 cluster with ND has received much attention recently, other nAChR subunit genes may play significant roles in the etiology of ND as well. For example, significant associations with various SNPs in CHRNA4 have been detected in at least three independent studies (Feng and others 2004; Hutchison and others 2007; Li and others 2005). Although no significant association of ND with CHRNB2 has been found in four independent studies (Feng and others 2004; Li and others 2005; Lueders and others 2002; Silverman and others 2000), recent research revealed that rs2072658 and rs2072661 in the 3′-UTR of CHRNB2 are associated with a reduced risk of smoking initiation, greater ability to quit smoking, and diminished early response to nicotine (Conti and others 2008; Ehringer and others 2007). Very recently, we showed a significant interaction between variants of CHRNA4 and CHRNB2 in affecting ND, concluding that CHRNB2 has a significant effect on ND when analyzed in interaction with CHRNA4. A smaller study in schizophrenic smokers suggested that CHRNA7 may be associated with smoking status (De Luca and others