Zhang Lan, Kendler Kenneth S, Chen Xiangning
Department of Psychiatry, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 Leigh Street, Suite 1-110, Richmond, VA 23298, USA.
Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141B(1):10-4. doi: 10.1002/ajmg.b.30240.
Since PTEN (phosphatase and tensin homolog) has elevated expression in rat brain (amygdala) after chronic administration of nicotine and the PTEN gene is located in the vicinity of the chromosome 10q23 linkage peak in a genome-scan study of nicotine dependence, PTEN seems a plausible candidate gene for smoking behavior. To test this hypothesis, we use a three-group case-control design and genotype five SNPs in the PTEN gene. We compare allele and genotype frequencies between the smokers and nonsmokers and between the low nicotine dependent and high nicotine dependent subjects. Three SNPs in the PTEN gene are significantly associated with smoking initiation (rs1234221, P = 0.0311; rs1234213, P = 0.0002; and rs2735343, P = 0.0028). Rs1234213 also shows association with nicotine dependence (P = 0.0278). Haplotype analyses indicate that a major haplotype, 1-1-2-2-1 for rs1234221-rs2299939-rs1234213-rs2735343-rs70184, is associated with smoking initiation. A minor haplotype (about 3%), 1-2-2-2-1 for the same five SNPs, is observed only in the high nicotine dependence group. These results suggest that the PTEN gene may be involved in the etiology of both smoking initiation and nicotine dependence.
由于在长期给予尼古丁后，PTEN（磷酸酶和张力蛋白同源物）在大鼠脑（杏仁核）中的表达升高，并且在一项关于尼古丁依赖的基因组扫描研究中，PTEN基因位于染色体10q23连锁峰附近，因此PTEN似乎是吸烟行为的一个合理候选基因。为了验证这一假设，我们采用三组病例对照设计，并对PTEN基因中的五个单核苷酸多态性（SNP）进行基因分型。我们比较了吸烟者与非吸烟者之间以及低尼古丁依赖者与高尼古丁依赖者之间的等位基因和基因型频率。PTEN基因中的三个SNP与开始吸烟显著相关（rs1234221，P = 0.0311；rs1234213，P = 0.0002；以及rs2735343，P = 0.0028）。Rs1234213也显示与尼古丁依赖有关（P = 0.0278）。单倍型分析表明，一个主要单倍型，即rs1234221 - rs2299939 - rs1234213 - rs2735343 - rs70184的1 - 1 - 2 - 2 - 1，与开始吸烟有关。仅在高尼古丁依赖组中观察到一个次要单倍型（约3%），即相同五个SNP的1 - 2 - 2 - 2 - 1。这些结果表明，PTEN基因可能参与了开始吸烟和尼古丁依赖的病因学。
