Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
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DOI：
10.1038/srep16301
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发表时间：
2015-11-06
影响因子：
4.6
通讯作者：
Bellivier, F.
中科院分区：
文献类型：
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作者：
Etain, B.;Lajnef, M.;Bellivier, F.
双相情感障碍（BD）的发病年龄（AAO）可能受到5-羟色胺转运体基因（SLC 6A 4）启动子区重复长度多态性（5 HTTLPR）和儿童期创伤的影响。我们评估了308例情感正常的BD患者的首次情绪发作和童年创伤的AAO。对患者进行5 HTTLPR（长/短变异）和rs 25531基因分型。基因型按功能显著性（LL、LS、SS）分类。126例巴西正常胸腺BD患者的样本用于复制。在法国样本中，AAO和创伤评分之间的相关性仅在“SS”纯合子中观察到（p = 0.002），但在“L”等位基因携带者中没有观察到。至少一次创伤史仅在“SS”纯合子中降低AAO（p = 0.001）。这些结果在使用FDR校正后仍然显著。回归模型表明情绪忽视和AAO上的“SS”基因型之间存在相互作用（p = 0.009），并且与其他创伤亚型没有进一步的相互作用。在巴西样本中获得了部分复制，显示情绪虐待和AAO上的“LS”基因型之间的相互作用（p = 0.02）。总之，儿童期创伤对BD的AAO的影响仅在携带特定应激反应相关SLC 6A 4启动子基因型的患者中观察到。
Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among 'SS' homozygotes (p = 0.002) but not among 'L' allele carriers. A history of at least one trauma decreased the AAO only in 'SS' homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and 'SS' genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and 'LS' genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype.