Anxiety Disorders Program, Hospital de Clínicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, Luiz Manoel Gonzaga, 630/11, 90470-280 Porto Alegre, RS, Brazil.
Neurosci Lett. 2010 Nov 12;485(1):11-5. doi: 10.1016/j.neulet.2010.08.042. Epub 2010 Sep 15.
The aim of this study is to evaluate the association between HTR1A, HTR2A and the 5-HTTLPR in panic disorder (PD) patients and controls. In addition, this study also aims to evaluate the interaction between these genes and two environmental factors previously associated with PD: childhood trauma and parental bonding.
This is a case-control candidate gene association study (107 PD patients and 125 controls). Genes were analyzed using a gene-based test in PLINK followed by single marker association tests and haplotype test only for genes that reached experiment-wide significance in the gene-based test in order to minimize multiple testing. Logistic regression was used to test the relationships between genotype in the additive model, trauma, optimal paternal parenting and optimal maternal parenting and their interactions.
Only HTR1A was associated with PD in gene-based test after correction for multiple tests (p(corrected)=0.027) and one HTR1A haplotype comprising four SNPs was associated with PD (p(corrected)=0.032). In the interaction analysis, no significant gene-environment interaction was found with the genes evaluated.
This study reinforces the association between HTR1A and PD. No major evidence of gene-environment interaction in PD with parenting or trauma was found. Further studies are necessary in order to confirm these findings.
本研究旨在评估惊恐障碍(PD)患者和对照者中 5-羟色胺转运体 1A(HTR1A)、5-羟色胺受体 2A(HTR2A)和 5-羟色胺转运体启动子区(5-HTTLPR)之间的关联。此外,本研究还旨在评估这些基因与两个先前与 PD 相关的环境因素:儿童期创伤和父母养育方式之间的相互作用。
这是一项病例对照候选基因关联研究(107 例 PD 患者和 125 例对照者)。采用 PLINK 中的基因基检测分析基因,然后仅对在基因基检测中达到实验范围显著的基因进行单标记关联检测和单倍型检测,以最大限度地减少多重检测。采用逻辑回归检验基因型在加性模型、创伤、最佳父性养育和最佳母性养育中的关系及其相互作用。
仅 HTR1A 在经过多测试校正后与 PD 相关(p(校正)=0.027),且包含四个 SNP 的一个 HTR1A 单倍型与 PD 相关(p(校正)=0.032)。在交互作用分析中,未发现所评估基因与养育或创伤之间存在显著的基因-环境相互作用。
本研究进一步证实了 HTR1A 与 PD 之间的关联。未发现 PD 与养育或创伤之间存在主要的基因-环境相互作用证据。需要进一步研究以确认这些发现。