Association of the tryptophan hydroxylase gene with smoking initiation butnot progression to nicotine dependence

We investigated the association between two markers in the seventh intron o f the tryptophan hydroxylase gene (TPH C218A and C779A) in a population-bas ed case control study of 780 genotyped subjects. As in prior studies, the t wo markers were in strong linkage disequilibrium, The phenotypes we studied were smoking initiation and progression to nicotine dependence. Allele, ge notype, and estimated haplotype frequencies for each marker were highly sig nificantly different for smoking initiation (P<0.0004 for each comparison) and were nonsignificant for progression to nicotine dependence. An empirica l test suggested that the positive results were unlikely to have resulted f rom population stratification. Our results are similar to those of Lerman e t al, [2001: Am J Med Genet (Neuropsychiatr Genet) 105:000-000] in associat ing these TPH markers with a construct related to smoking initiation but di ssimilar in the variable implicated. If these results replicate in other sa mples, the serotonergic system may be involved in the etiology of smoking i nitiation given the rate-limiting role of TPH in the biosynthesis Of seroto nin. (C) 2001 Wiley-Liss, Inc.