Department of Psychology, University of California, Los Angeles, 90095-1563, USA.
Depress Anxiety. 2010 Aug;27(8):737-45. doi: 10.1002/da.20715.
Investigations of gene-environment interaction (GxE) in depression have implicated a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the stress-depression relationship. However, recent evidence for 5-HTTLPR GxE in depression has been inconsistent. This study examined the moderating effect of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene on the strength of 5-HTTLPR GxE.
A community sample of youth (n=384) was genotyped for 5-HTTLPR and COMT. A multi-method, multi-informant index of chronic family stress was derived from interviews and questionnaires administered at youth age 15. GxGxE was examined in relation to depression diagnoses between ages 15 and 20 and depressive symptoms at age 20.
Significant three-way interactions were observed for both depressive symptoms and diagnoses, such that 5-HTTLPR GxE occurred only in the context of COMT val158 allele homozygosity. For val158 homozygotes, the 5-HTTLPR LL genotype exerted a protective effect in the face of stress. No genetic main effect or two-way GxE was found for 5-HTTLPR.
Inconsistent 5-HTTLPR GxE findings to date may be partly attributable to unmeasured epistatic effects between 5-HTTLPR and COMT val158met. Identifying the conditions under which 5-HTTLPR GxE is most likely to operate may allow depression prevention and treatment efforts to target youth at highest risk.
对抑郁症中基因-环境相互作用（GxE）的研究表明，5-羟色胺转运体基因（5-HTTLPR）启动子区域的一个多态性是应激-抑郁关系的调节剂。然而，最近关于 5-HTTLPR GxE 在抑郁症中的证据并不一致。本研究检验了儿茶酚-O-甲基转移酶（COMT）基因中的 val158met 多态性对 5-HTTLPR GxE 强度的调节作用。
对青年社区样本（n=384）进行 5-HTTLPR 和 COMT 基因分型。采用访谈和问卷调查，从青少年 15 岁时获得多方法、多信息的慢性家庭应激指数。在 15 岁至 20 岁期间检查 GxGxE 与抑郁诊断的关系，以及 20 岁时的抑郁症状。
观察到抑郁症状和诊断均存在显著的三向交互作用，表明仅在 COMT val158 等位基因纯合的情况下才会发生 5-HTTLPR GxE。对于 val158 纯合子，5-HTTLPR LL 基因型在面临应激时具有保护作用。未发现 5-HTTLPR 的遗传主效应或双向 GxE。
迄今为止，5-HTTLPR GxE 的不一致发现可能部分归因于 5-HTTLPR 和 COMT val158met 之间未测量的上位效应。确定 5-HTTLPR GxE 最有可能发生的条件可能使预防和治疗抑郁症的努力能够针对风险最高的青年。
