Sullivan P F, Jiang Y, Neale M C, Kendler K S, Straub R E
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Am J Med Genet. 2001 Jul 8;105(5):479-84. doi: 10.1002/ajmg.1433.
We investigated the association between two markers in the seventh intron of the tryptophan hydroxylase gene (TPH C218A and C779A) in a population-based case control study of 780 genotyped subjects. As in prior studies, the two markers were in strong linkage disequilibrium. The phenotypes we studied were smoking initiation and progression to nicotine dependence. Allele, genotype, and estimated haplotype frequencies for each marker were highly significantly different for smoking initiation (P < 0.0004 for each comparison) and were nonsignificant for progression to nicotine dependence. An empirical test suggested that the positive results were unlikely to have resulted from population stratification. Our results are similar to those of Lerman et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:000-000] in associating these TPH markers with a construct related to smoking initiation but dissimilar in the variable implicated. If these results replicate in other samples, the serotonergic system may be involved in the etiology of smoking initiation given the rate-limiting role of TPH in the biosynthesis of serotonin.
在一项针对780名基因分型受试者的基于人群的病例对照研究中，我们调查了色氨酸羟化酶基因第七内含子中的两个标记（TPH C218A和C779A）之间的关联。与先前的研究一样，这两个标记处于强连锁不平衡状态。我们研究的表型是开始吸烟和发展为尼古丁依赖。每个标记的等位基因、基因型和估计单倍型频率在开始吸烟方面存在高度显著差异（每次比较P < 0.0004），而在发展为尼古丁依赖方面不显著。一项实证检验表明，阳性结果不太可能是由人群分层导致的。我们的结果与Lerman等人[2001年：《美国医学遗传学杂志》（神经精神遗传学）105:000 - 000]的结果相似，即将这些TPH标记与与开始吸烟相关的一个结构联系起来，但在所涉及的变量方面有所不同。如果这些结果能在其他样本中得到重复，鉴于色氨酸羟化酶在血清素生物合成中的限速作用，血清素能系统可能参与了开始吸烟的病因学。
