Wang Tzu-Yun, Lee Sheng-Yu, Chen Shiou-Lan, Chang Yun-Hsuan, Chen Shih-Heng, Huang San-Yuan, Tzeng Nian-Sheng, Wang Chen-Lin, Yeh Pin-Hsi, Chen Kao Chin, Lee I Hui, Yeh Tzung Lieh, Yang Yen Kuang, Lu Ru-Band
Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan.
Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Int J Neuropsychopharmacol. 2014 Feb;17(2):211-22. doi: 10.1017/S1461145713001296. Epub 2013 Nov 12.
Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5-HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.
关于双相情感障碍发病风险与血清素转运体关联多态性区域基因（5-HTTLPR）及多巴胺D2受体基因（DRD2）变体功能之间的关联研究结果相互矛盾。对此的一种解释是，基因贡献可能存在性别差异。我们比较了成年I型双相障碍（BP-I）和II型双相障碍（BP-II）男性和女性患者中血清素转运体基因（SLC6A4）与DRD2之间的性别相关主效应以及基因-基因相互作用。BP-I患者（n = 400）、BP-II患者（n = 493）以及健康对照者（n = 442）均来自台湾汉族人群。采用聚合酶链反应-限制性片段长度多态性分析确定5-HTTLPR和DRD2 Taq-IA多态性的基因型。逻辑回归分析显示，DRD2 A1/A1以及5-HTTLPR S/S、S/LG和LG/LG（S+）基因型在BP-I男性患者（p分别为0.002和0.01）和BP-II男性患者（p分别为0.001和0.007）中存在显著的性别特异性关联，但在女性患者中不存在。仅在BP-I和BP-II男性患者中还发现DRD2 A1/A1与5-HTTLPR S+多态性之间存在显著相互作用（p分别为0.003和0.001）。我们提供了初步证据，证明SLC6A4和DRD2基因变体对BP-I和BP-II风险存在性别特异性影响。我们还发现双相情感障碍患者中5-HTTLPR与DRD2 Taq-IA多态性之间存在性别特异性相互作用。
