The interaction of early life experiences with COMT val158met affects anxiety sensitivity
The interaction of early life experiences with COMT val158met affects anxiety sensitivity
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DOI：
10.1111/gbb.12090
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发表时间：
2013-11-01
影响因子：
2.5
通讯作者：
Reif, A.
中科院分区：
文献类型：
--
作者：
Baumann, C.;Klauke, B.;Reif, A.
焦虑症的发病机制被认为是多因素的，具有遗传因素和个体环境因素的复杂相互作用。因此，本研究的目的是研究基因的环境相互作用的基因编码的儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶A（MAOA）与生活事件的措施有关的焦虑。对健康受试者的样本（N=782;其中531名女性;平均年龄M=24.79，SD=6.02）进行COMT rs 4680和MAOA-uVNTR（上游可变数目串联重复序列）的基因分型，并评估儿童期逆境[儿童期创伤问卷（CTQ）]、焦虑敏感性[焦虑敏感性指数（ASI）]和焦虑忧虑[宾夕法尼亚州立大学焦虑问卷（PSWQ）]。通过回归分析评估了基因型、环境和性别对焦虑相关指标的主效应和交互效应。关联分析表明，没有主基因的影响，无论是问卷得分。观察到儿童期逆境和COMT基因型的显著交互作用：低活性met等位基因和高CTQ得分的纯合性与解释的ASI方差的显著增加相关[R-2=0.040，错误发现率（FDR）校正P=0.04]。关于MAOA-uVNTR的临界交互作用仅限于男性亚组。携带低活性MAOA等位基因的儿童在童年时报告了更多令人厌恶的经历，表现出增强焦虑恐惧的趋势（R-2=0.077，FDR校正P=0.10）。因此，在COMT 158 met等位基因或低活性MAOA-uVNTR等位基因纯合性存在的情况下，早期厌恶的生活经历可能会增加焦虑症的易感性。
The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N=782; thereof 531 women; mean age M=24.79, SD=6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R-2=0.040, false discovery rate (FDR) corrected P=0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R-2=0.077, FDR corrected P=0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles.