Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study.
Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study.
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DOI：
10.1371/journal.pone.0039184
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Uddin M
中科院分区：
文献类型：
--
作者：
Chang SC;Koenen KC;Galea S;Aiello AE;Soliven R;Wildman DE;Uddin M
最近的研究表明，位于SLC 6A 3基因3′UTR VNTR的9-重复（9 R）等位基因增加了创伤后应激障碍（PTSD）的风险。然而，迄今为止，没有研究报告这种关联是基于基于人群的样本。此外，我们所知道的研究还没有评估SLC 6A 3基因和DNA甲基化变异对PTSD风险的联合作用。在这项研究中，我们评估了SLC 6A 3基因座的分子变异是否影响PTSD的风险。参与者（n = 320; 62例/258例对照）来自底特律主要为非洲裔美国人的城市社区样本，包括完成基线电话调查、提供血液标本、具有9 R或10 R等位基因纯合基因型或杂合9 R/10 R基因型的人。SLC 6A 3启动子基因座的DNA甲基化变异的影响也在一组有可用甲基化数据的参与者中进行了评估（n = 83; 16例/67例对照）。 在完整的分析样本中，9 R等位基因携带者与10 R/10 R基因型携带者相比，终生PTSD的风险几乎增加一倍（OR = 1.98，95%CI = 1.02-3.86），控制年龄，性别，种族，社会经济状况，创伤次数，吸烟和终生抑郁症。 在具有可用甲基化数据的参与者的子样本中，观察到显著（p = 0.008）的相互作用，其中9 R等位基因携带者仅在与SLC 6A 3启动子基因座的高甲基化结合时显示出终生PTSD的风险增加，控制相同的协变量。 我们的研究结果证实了以前的报告支持的作用，9 R等位基因在增加易感性创伤后应激障碍。他们进一步扩展了这些发现，提供了初步证据，即“双重打击”模型，包括pured-reduced-function allele和启动子区域的高甲基化，可以更准确地捕获SLC 6A 3基因座的PTSD分子风险。
Recent work suggests that the 9-repeat (9R) allele located in the 3′UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on population-based samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02–3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a “double hit” model, including both a putatively reduced-function allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus.
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DOI：
10.1002/ajmg.b.10948
发表时间：
2002-12-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Mill, J;Asherson, P;Craig, I
通讯作者：
Craig, I
影响因子：
3.3
作者：
Drury, Stacy S.;Theall, Katherine P.;Keats, Bronya J. B.;Scheeringa, Michael
通讯作者：
Scheeringa, Michael
DOI：
10.1002/ajmg.b.30572
发表时间：
2007-12-05
影响因子：
2.8
作者：
Brookes, Keeley J.;Neale, Benjamin M.;D'Souza, Ursula M.
通讯作者：
D'Souza, Ursula M.
影响因子：
7.7
作者：
Neugebauer, Richard;Fisher, Prudence W.;Stehling-Ariza, Tasha
通讯作者：
Stehling-Ariza, Tasha
影响因子：
10.6
作者：
Kolassa, Iris-Tatjana;Kolassa, Stephan;De Quervain, Dominique J. -F.
通讯作者：
De Quervain, Dominique J. -F.