Calabrò Marco, Mandelli Laura, Crisafulli Concetta, Sidoti Antonella, Jun Tae-Youn, Lee Soo-Jung, Han Changsu, Patkar Ashwin A, Masand Prakash S, Pae Chi-Un, Serretti Alessandro
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
Neuropsychobiology. 2016;74(3):159-168. doi: 10.1159/000468543. Epub 2017 May 12.
Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning.
One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested.
Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7.
Limited sample size and risk of false-positive findings.
Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.
双相情感障碍（BPD）是一种常见且严重的精神障碍。遗传因素在双相情感障碍的病理生理学中的作用已广为人知。在本研究中，我们检测了3个强候选基因（CACNA1C、CHRNA7和MAPK1）内的几个单核苷酸多态性（SNP）与双相情感障碍的关联。这些基因参与单胺相关途径，以及树突发育、神经元存活、突触可塑性和记忆/学习。
对132名被诊断为双相情感障碍的受试者和326名韩国血统的健康对照者进行CACNA1C、CHRNA17和MAPK1内40个SNP的基因分型。比较病例组和对照组中每个基因内等位基因的分布和单倍型块。还检测了不同位点变体之间的相互作用。
在病例组和对照组之间，检测到CACNA1C内的rs1016388、CHRNA7内的rs1514250、rs2337980、rs6494223、rs3826029和rs4779565以及MAPK1内的rs8136867的等位基因分布存在显著差异。单倍型分析也证实了这些基因内的变异与双相情感障碍有关。最后，探索性上位性分析显示了潜在的交互作用，特别是关于CACNA1C和CHRNA7的变异。
样本量有限以及存在假阳性结果的风险。
我们的数据表明这3个基因在双相情感障碍中可能起作用。一个或多个常见脑通路（如神经发育和神经可塑性、钙信号传导）的改变可能解释所获得的结果。
