Kotyuk Eszter, Keszler Gergely, Nemeth Nora, Ronai Zsolt, Sasvari-Szekely Maria, Szekely Anna
Doctoral School of Psychology, Eötvös Loránd University, Budapest, Hungary ; Institute of Psychology, Eötvös Loránd University, Budapest, Hungary.
PLoS One. 2013 Dec 6;8(12):e80613. doi: 10.1371/journal.pone.0080613. eCollection 2013.
Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for dopaminergic neurons with promising therapeutic potential in Parkinson's disease. A few association analyses between GDNF gene polymorphisms and psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and drug abuse have also been published but little is known about any effects of these polymorphisms on mood characteristics such as anxiety and depression. Here we present an association study between eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide polymorphisms (SNPs) and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no psychiatric history. Results of the allele-wise single marker association analyses provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p = 0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively), while no such result was obtained on depression scores. Haplotype analysis confirmed the role of these SNPs; mean anxiety scores raised according to the number of risk alleles present in the haplotypes (p = 0.00029). A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. In conclusion, this is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140) and individual variability of anxiety using self-report data from a non-clinical sample.
胶质细胞源性神经营养因子（GDNF）是一种针对多巴胺能神经元的神经营养因子，在帕金森病治疗中具有潜在的应用前景。此前也有一些关于GDNF基因多态性与精神疾病（如精神分裂症、注意力缺陷多动障碍和药物滥用）之间的关联分析报道，但这些多态性对焦虑和抑郁等情绪特征的影响却知之甚少。在此，我们对708名无精神病史的白种年轻成年人进行了一项关联研究，分析了胶质细胞源性神经营养因子的8个单核苷酸多态性（SNPs，分别为rs1981844、rs3812047、rs3096140、rs2973041、rs2910702、rs1549250、rs2973050和rs11111）与采用医院焦虑抑郁量表（HADS）测量的焦虑和抑郁得分之间的关系。在对多重检验进行Bonferroni校正后，等位基因层面的单标记关联分析结果显示，两个单核苷酸多态性对焦虑得分有显著影响（rs3812047和rs3096140的p值分别为0.00070和0.00138），而在抑郁得分方面未得到类似结果。单倍型分析证实了这些SNPs的作用；根据单倍型中存在的风险等位基因数量，平均焦虑得分升高（p = 0.00029）。还观察到显著的性别-基因相互作用，因为rs3812047 A等位基因作为焦虑风险因素的作用在男性中更为明显。总之，这是首次通过非临床样本的自我报告数据，证明GDNF基因的两个SNP（rs3812047和rs3096140）与焦虑个体差异之间的关联，从而证实了GDNF基因与情绪特征之间存在显著关联。
