Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment.
Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment.
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DOI：
10.2147/ndt.s29508
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发表时间：
2012
影响因子：
3.2
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Boscarino JA;Erlich PM;Hoffman SN;Zhang X
该研究的目的是评估位于四个遗传位点内的多态性的累积负担，这些基因位点以前与创伤后应激障碍（PTSD）在有PTSD风险的门诊患者中相关。在412名疼痛患者中完成诊断访谈并收集DNA样本，以确定FKBP 5（rs 9470080），COMT（rs 4680），CHRNA 5（rs 16969968）和CRHR 1（rs 110402）单核苷酸多态性是否与PTSD风险增加累积相关。在双变量分析中，发现位于FKBP 5、COMT、CHRNA 5和CRHR 1基因座内的特定PTSD风险等位基因的计数（等位基因范围= 0-6，平均计数= 2.92，标准差= 1.36）与寿命相关（t [409] = 3.430，P = 0.001）和早发性创伤后应激障碍（t [409] = 4.239，P = 0.000028）。在logistic回归中，控制人口统计学因素，人格特质和创伤暴露，这种风险等位基因计数仍然与终身（比值比= 1.49，P = 0.00158）和早发性PTSD（比值比= 2.36，P = 0.000093）。交互作用也被检测到，即具有较高风险等位基因计数和较高创伤暴露的个体在这些logistic回归中终生PTSD（等位基因计数×高创伤，P = 0.026）和早发性PTSD（等位基因计数×高创伤，P = 0.016）的风险增加。那些没有或很少有风险等位基因的人似乎对PTSD有弹性，无论暴露史如何。涉及位于FKBP 5、COMT、CHRNA 5和CRHR 1基因内的四个单核苷酸多态性的累积风险等位基因计数与PTSD相关。创伤暴露水平与危险等位基因计数相互作用，因此PTSD在具有较高危险等位基因计数和较高创伤暴露的人中增加。由于研究的单核苷酸多态性包括压力回路和成瘾生物学，这些发现可能对神经精神研究和治疗有影响。
The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD) among outpatients at risk for PTSD. Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080), COMT (rs4680), CHRNA5 (rs16969968), and CRHR1 (rs110402) single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD. In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36) was associated with lifetime (t [409] = 3.430, P = 0.001) and early onset PTSD (t [409] = 4.239, P = 0.000028). In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158) and early onset PTSD (odds ratio = 2.36, P = 0.000093). Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026) and early onset PTSD (allele count × high trauma, P = 0.016) in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history. A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.