Campos Simone Becho, Miranda Débora M, Souza Bruno R, Pereira Patricia A, Neves Fernando S, Tramontina Juliana, Kapczinski Flávio, Romano-Silva Marco Aurélio, Correa Humberto
Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Laboratório de Neurociências e Genética Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Psychiatr Genet. 2011 Apr;21(2):106-11. doi: 10.1097/YPG.0b013e328341a3a8.
Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.
在临床和流行病学研究中，广泛报道了惊恐障碍（PD）与心境障碍之间频繁的共病现象，并且最近，人们越来越关注PD与双相情感障碍（BD）的共病情况。多项研究表明，血清素活性失衡可能与惊恐症状有关。色氨酸羟化酶2（TPH2）可能是与PD相关的候选基因。本研究的目的是调查TPH2基因多态性与PD共病易感性之间可能存在的关联。我们的样本包括515名患者；274名BD患者（I型和II型亚型），其中包括45名有终生惊恐障碍共病的患者以及241名对照。对这些患者进行了人类TPH2基因的8个标签单核苷酸多态性的基因分型。我们发现，在等位基因分析（rs4448731，P = 0.0069；rs4565946，P = 0.0359；rs4760820，P = 0.0079；rs1487275，P = 0.0439）和基因型分析（rs4448731，P = 0.011；rs4760820，P = 0.0259）中，有惊恐障碍共病的BD患者与对照之间存在显著差异。我们还发现在等位基因分析（rs4448731，P = 0.004；rs4565946，P = 0.011；rs11179000，P = 0.031；rs4760820，P = 0.018；rs1487275，P = 0.038；rs10879357，P = 0.023）和基因型分析（rs4448731，P = 0.004；rs4565946，P = 0.010；rs4760820，P = 0.023；rs10879357，P = 0.052）中，有和没有惊恐障碍共病的BD患者之间存在显著差异。在有和没有惊恐障碍共病的BD患者组中的单倍型分析也具有显著性（rs4448731 - rs4565946，P = 0.0190；rs4448731 - rs4565946，P = 0.0220；rs10506645 - rs4760820，P = 0.0360）。需要进一步的研究来重复我们观察到的阳性关联。
