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Chunk #3 — INTRODUCTION

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Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes.
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The muscle-type nicotinic receptor is composed of two alpha subunits, one beta, one delta and either one gamma or one epsilon subunit (Karlin, 2002). Neuronal-type receptors can be homopentamers or heteropentamers. The predominant heteropentameric nAChRs are α4β2* in brain and α3β4* in the peripheral nervous system (Gotti et al., 2006; Mao et al., 2006). In some instances, other subunits (as indicated by the asterisk), principally α5, also contribute to these two major heteromeric receptor subtypes. The α7 subunit is the only nAChR subunit confirmed to form homomeric nAChRs in mammalian brain (Chen and Patrick, 1997). The dopamine reward pathway, which is thought to play a critical role in addiction, is modulated by multiple nAChR subtypes, including α4β2, α4β2α5, α6β2β3, α4α6β2β3, and α7 (Klink et al., 2001; Pidoplichko et al., 2004; Salminen et al., 2004; Wooltorton et al., 2003; Wu et al., 2004).