Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 954 Gatewood Drive, Atlanta, GA 30329, USA.
Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):812-24. doi: 10.1002/ajmg.b.31052.
Gene x environment (G x E) interactions mediating depressive symptoms have been separately identified in the stress-sensitive serotonergic (5-HTTLPR) and corticotropin-releasing hormone (CRHR1) systems. Our objective was to examine whether the effects of child abuse are moderated by gene x gene (G x G) interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association study examining G x G x E interactions of CRHR1 and 5-HTTLPR polymorphisms and measures of child abuse on adult depressive symptomatology. The participant population (N = 1,392) was African-American, of low socioeconomic status (60% with <$1,000/month family income), and with high rates of childhood and lifetime trauma. Depressive symptoms were measured with Beck Depression Inventory (BDI) and history of Major Depression by Structure Clinical Interview based on DSM-IV (SCID). We first replicated an interaction of child abuse and 5-HTTLPR on lifetime SCID diagnosis of major depression in a subsample (N = 236) of the study population-the largest African-American 5-HTTLPR cohort reported to date. We then extended our previously reported interaction with both a CRHR1 SNP (rs110402) and TCA haplotype interacting with child abuse to predict current symptoms (N = 1,059; P = 0.0089). We found that the 5-HTTLPR S allele interacted with CRHR1 haplotypes and child abuse to predict current depressive symptoms (N = 856, P = 0.016). These data suggest that G x E interactions predictive of depressive symptoms may be differentially sensitive to levels of childhood trauma, and the effects of child abuse are moderated by genetic variation at both the CRHR1 and 5-HTTLPR loci and by their G x G interaction.
基因与环境（G×E）相互作用分别在应激敏感的 5-羟色胺（5-HTTLPR）和促肾上腺皮质激素释放激素（CRHR1）系统中被识别出来。我们的目的是研究 CRHR1 和 5-HTTLPR 多态性之间的基因与基因（G×G）相互作用是否调节了儿童虐待的影响。我们使用了一项关联研究，研究了 CRHR1 和 5-HTTLPR 多态性与儿童虐待对成人抑郁症状的影响，以及 G×G×E 相互作用。研究对象为非洲裔美国人，社会经济地位较低（60%的家庭月收入低于 1000 美元），儿童期和终生创伤发生率较高。抑郁症状采用贝克抑郁量表（BDI）和基于 DSM-IV 的结构临床访谈（SCID）进行评估。我们首先在研究人群的一个亚组（N=236）中复制了儿童虐待与 5-HTTLPR 对终生 SCID 诊断的影响，这是迄今为止报道的最大的非洲裔 5-HTTLPR 队列。然后，我们扩展了我们之前报道的与 CRHR1 SNP（rs110402）和与儿童虐待相互作用的 TCA 单倍型的相互作用，以预测当前症状（N=1059；P=0.0089）。我们发现，5-HTTLPR S 等位基因与 CRHR1 单倍型和儿童虐待相互作用，可预测当前的抑郁症状（N=856，P=0.016）。这些数据表明，预测抑郁症状的 G×E 相互作用可能对儿童期创伤的程度有不同的敏感性，而儿童虐待的影响受到 CRHR1 和 5-HTTLPR 基因座遗传变异及其 G×G 相互作用的调节。
