Center for Health Research, Geisinger Clinic, Danville, PA.
Neuropsychiatr Dis Treat. 2012;8:131-9. doi: 10.2147/NDT.S29508. Epub 2012 Mar 23.
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.
本研究旨在评估先前与创伤后应激障碍（PTSD）相关的四个遗传位点内的多态性在 PTSD 高危门诊患者中的累积负担。
对 412 名疼痛患者进行诊断性访谈并采集 DNA 样本，以确定 FKBP5（rs9470080）、COMT（rs4680）、CHRNA5（rs16969968）和 CRHR1（rs110402）单核苷酸多态性是否与 PTSD 风险增加有关。
在双变量分析中，发现 FKBP5、COMT、CHRNA5 和 CRHR1 遗传位点内特定 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）与终生（t[409]=3.430，P=0.001）和早期 PTSD（t[409]=4.239，P=0.000028）有关。在逻辑回归中，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与终生（优势比=1.49，P=0.00158）和早期 PTSD（优势比=2.36，P=0.000093）有关。还检测到了交互效应，即在这些逻辑回归中，具有较高风险等位基因计数和较高创伤暴露的个体，患终生 PTSD（等位基因计数×高创伤，P=0.026）和早期 PTSD（等位基因计数×高创伤，P=0.016）的风险增加。那些没有或只有少数风险等位基因的人对 PTSD 具有弹性，无论暴露史如何。
涉及 FKBP5、COMT、CHRNA5 和 CRHR1 基因内四个单核苷酸多态性的累积风险等位基因计数与 PTSD 有关。创伤暴露水平与风险等位基因计数相互作用，使得具有较高风险等位基因计数和较高创伤暴露的个体 PTSD 增加。由于所研究的单核苷酸多态性涵盖了应激回路和成瘾生物学，这些发现可能对神经精神学研究和治疗有意义。
