Laboratory of Psychoneuroendocrinology and Molecular Genetics. Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain.
World J Biol Psychiatry. 2011 Aug;12(5):376-84. doi: 10.3109/15622975.2011.552192. Epub 2011 May 19.
OBJECTIVES. Recent studies have evidenced that bipolar patients show a sensory gating deficit (P50). Among the neural systems that could be influencing this electrophysiological phenotype, dopamine seems to play an important role. We hypothesize that catechol-O-methyltransferase (COMT), the main metabolizer of dopamine in prefrontal cortex, is related to this deficit. METHODS. We selected three polymorphisms in COMT gene: rs2075507 (Promoter 2 region), Val158Met (rs4680) and rs165599 (3' region). A case-control study was performed in 784 controls and 238 bipolar patients. Besides, 122 euthymic bipolar subjects and 95 healthy subjects carried out a sensory gating task (P50). RESULTS. Polymorphism rs165599 in the COMT gene was associated with susceptibility to bipolar disorder (BD), mainly in women (AG: OR = 1.46; GG: OR = 1.84; P = 0.03). In the female group, haplotype AAG was associated with an OR = 7.6. Subjects who carried Val158 allele evidenced a deficit in suppression (P = 0.046) and rs165599 allele G carriers (mainly in homozygosis) had a bigger S2 amplitude and a higher S2/S1 ratio (1.6(e-5) < P < 0.01). Not a single association was proven in the control group. CONCLUSIONS. Our results support the association of the COMT gene with BD and with one of its potential endophenotypes, auditory sensory gating deficit, measured by the P50 paradigm.
目的。最近的研究表明，双相情感障碍患者存在感觉门控缺陷（P50）。在可能影响这种电生理表型的神经系统中，多巴胺似乎起着重要作用。我们假设儿茶酚-O-甲基转移酶（COMT），即前额叶皮层中多巴胺的主要代谢物，与这种缺陷有关。方法。我们选择了 COMT 基因中的三个多态性：rs2075507（启动子 2 区）、Val158Met（rs4680）和 rs165599（3'区）。在 784 名对照和 238 名双相情感障碍患者中进行了病例对照研究。此外，122 名双相情感障碍患者和 95 名健康对照进行了感觉门控任务（P50）。结果。COMT 基因中的 rs165599 多态性与双相情感障碍（BD）的易感性有关，主要与女性有关（AG：OR=1.46；GG：OR=1.84；P=0.03）。在女性组中，AAG 单体型与 OR=7.6 相关。携带 Val158 等位基因的受试者表现出抑制缺陷（P=0.046），而 rs165599 等位基因 G 携带者（主要为纯合子）的 S2 振幅更大，S2/S1 比值更高（1.6(e-5)<P<0.01）。在对照组中没有证明任何关联。结论。我们的结果支持 COMT 基因与 BD 及其潜在的表型之一，即通过 P50 范式测量的听觉感觉门控缺陷有关。
