Phenotypic Effects of a Bipolar Liability Gene Among Individuals With Major Depressive Disorder
Phenotypic Effects of a Bipolar Liability Gene Among Individuals With Major Depressive Disorder
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DOI：
10.1002/ajmg.b.30962
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发表时间：
2010-01-01
影响因子：
2.8
通讯作者：
Perlis, Roy H.
中科院分区：
文献类型：
--
作者：
Casamassima, Francesco;Huang, Jie;Perlis, Roy H.
在最近的全基因组关联研究的荟萃分析中，电压依赖性钙通道 L 型 α 1C 亚基 (CACNA1C) 基因的变异与躁郁症相关 [Ferreira et al., 2008]。这些变异对其他精神疾病的影响尚未得到研究。抑郁症治疗 STAR(star)D 研究中可获得 DNA 的白人非西班牙裔参与者 (N = 1213) 对 CACNA1C 基因中的两个单核苷酸多态性 (SNP)（rs10848635 和 rs1006737）进行了基因分型。我们检查了重度抑郁症患者双相情感障碍的假定表型指标以及暗示潜在双相情感障碍的纵向病程要素。我们还考虑了西酞普兰治疗后的缓解和抑郁严重程度。 rs10848635 风险等位基因与较低水平的基线躁动显着相关（P = 0.03；β = -0.09）。 rs1006737 风险等位基因与较低的基线抑郁严重程度（P = 0.04；β = -0.4）和失眠可能性降低（P = 0.047；β = -0.22）显着相关。这两种标志物均与西酞普兰引起的自杀风险增加相关（rs10848635：OR = 1.29，P = 0.04；rs1006737：OR = 1.34，P = 0.02）。在这项探索性分析中，治疗引起的自杀与假定的双相情感倾向基因中的两个风险等位基因相关。 (C) 2009 Wiley-Liss, Inc.
Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR(star)D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citaloprain treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene. (C) 2009 Wiley-Liss, Inc.