Departamento de Biologia Geral, Instituto de Biologia, Universidade Federal Fluminense (UFF), Niterói, Brazil.
Programa de Transtornos Obsessivo-Compulsivos e de Ansiedade, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Compr Psychiatry. 2018 Apr;82:1-6. doi: 10.1016/j.comppsych.2017.12.004. Epub 2017 Dec 16.
Obsessive-Compulsive Disorder (OCD) is a complex and chronic disorder characterized by recurrent thoughts and/or repetitive behaviors. Given the potent anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes related to serotonergic system may be well implicated in the etiopathogenesis of OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been previously associated with OCD. Additionally, the serotonin 2A receptor gene (HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have also been overrepresented among OCD patients. Therefore, the aim of this study is to evaluate the association of these three polymorphisms with OCD, through the examination of potential sources of heterogeneity in previous studies including age of onset, sex and symptom dimensions.
Polymorphisms were genotyped by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205 healthy controls from Brazil.
Although we did not observe any statistically significant association between the HTR2A gene polymorphisms and OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more common among OCD patients as compared to health controls. Further, a significant association between the STin2.12 allele and OCD, as well as a dominant effect of the STin2.12 allele in OCD was seen. Of note, late-onset (>18years) OCD was significantly more often seen in association with homozygosis for STin2.12 allele. No significant associations were observed with different OCD symptom dimensions.
Our results indicate an important influence of the STin2 polymorphism in OCD, but more studies are warranted to confirm these results.
强迫症（OCD）是一种复杂且慢性的障碍，其特征为反复出现的想法和/或重复行为。鉴于所谓的血清素再摄取抑制剂具有强大的抗强迫作用，与血清素能系统相关的基因可能与 OCD 的发病机制密切相关。编码血清素转运体（SLC6A4）的基因在 2 号内含子（STin2）中存在可变数量串联重复（VNTR）多态性，先前与 OCD 相关。此外，5-羟色胺 2A 受体基因（HTR2A）有两个多态性（A-1438G - rs6311 和 T102C - rs6313），在 OCD 患者中也有过表达。因此，本研究旨在通过检查以前研究中包括发病年龄、性别和症状维度在内的潜在异质性来源，评估这三种多态性与 OCD 的相关性。
通过聚合酶链反应（PCR）在来自巴西的 203 名 OCD 患者和 205 名健康对照者的样本中检测多态性。
尽管我们没有观察到 HTR2A 基因多态性与 OCD 或其临床特征之间存在任何统计学上的显著关联，但 SLC6A4 STin2 多态性在 OCD 患者中比健康对照组更为常见。此外，还观察到 STin2.12 等位基因与 OCD 之间存在显著关联，以及 STin2.12 等位基因在 OCD 中的显性作用。值得注意的是，迟发性（>18 岁）OCD 与 STin2.12 等位基因纯合子显著相关。不同 OCD 症状维度未见显著相关性。
我们的研究结果表明 STin2 多态性在 OCD 中具有重要影响，但需要更多的研究来证实这些结果。
