1] Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA [2] Mood and Anxiety Disorders Section, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Pharmacogenomics J. 2013 Oct;13(5):464-9. doi: 10.1038/tpj.2012.33. Epub 2012 Aug 21.
Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder (GAD). We examined a possible interaction between the serotonin transporter gene (SLC6A4) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene (HTR2A) single-nucleotide polymorphism (SNP) rs7997012 in antidepressant treatment outcome in GAD. Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes obtained for the 5-HTTLPR/rs25531 (La/La, La/S or S/S) haplotype and rs7997012 SNP (G or A) in the European American population (n=112) were used for pharmacogenetic analysis. Our data show that subjects with genotypes La/La+G/G or La/La+G/A (n=28) had significantly lower Hamilton Anxiety Scale (HAM-A) scores than those with genotypes La/S+A/A or S/S+A/A (n=12) at 6 months (HAM-A difference=10.7; P<0.0001). Single-marker analysis only showed HAM-A differences of 4.3 (5-HTTLPR/rs25531: La/La versus La/S+S/S) and 4.8 (rs7997012: G/G+G/A versus A/A), showing for the first time a significant gene-gene interaction between these markers.
基因在血清素能信号传导中的变异被认为与广泛性焦虑障碍（GAD）的抗抑郁治疗反应有关。我们研究了血清素转运蛋白基因（SLC6A4）5-HTTLPR/rs25531 单倍型与 5-羟色胺 2A 受体基因（HTR2A）单核苷酸多态性（SNP）rs7997012 在 GAD 抗抑郁治疗结果中的可能相互作用。被诊断患有 GAD 的患者接受文拉法辛 XR 治疗，作为 18 个月复发预防研究的一部分。在欧洲裔美国人（n=112）中获得了 5-HTTLPR/rs25531（La/La、La/S 或 S/S）单倍型和 rs7997012 SNP（G 或 A）的基因型，用于药物遗传学分析。我们的数据表明，基因型为 La/La+G/G 或 La/La+G/A（n=28）的患者在 6 个月时的汉密尔顿焦虑量表（HAM-A）评分显著低于基因型为 La/S+A/A 或 S/S+A/A（n=12）的患者（HAM-A 差值=10.7；P<0.0001）。单标记分析仅显示 HAM-A 的差异为 4.3（5-HTTLPR/rs25531：La/La 与 La/S+S/S）和 4.8（rs7997012：G/G+G/A 与 A/A），这是首次表明这些标记物之间存在显著的基因-基因相互作用。
