Calabrò Marco, Mandelli Laura, Crisafulli Concetta, Lee Soo-Jung, Jun Tae-Youn, Wang Sheng-Min, Patkar Ashwin A, Masand Prakash S, Han Changsu, Pae Chi-Un, Serretti Alessandro
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina.
Clin Psychopharmacol Neurosci. 2019 Aug 31;17(3):364-368. doi: 10.9758/cpn.2019.17.3.364.
Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage- gated channel subunit alpha1 C ( CACNA1C ), cholinergic receptor nicotinic alpha 7 subunit ( CHRNA7 ), and mitogen- activated protein kinase 1 ( MAPK1 ).
Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C , CHRNA7 , and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms' severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed.
Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment.
These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.
遗传因素可能在重度抑郁症（MDD）的风险、临床表现及治疗结果中发挥作用。在本研究中，我们调查了三个MDD候选基因的作用，即钙电压门控通道α1C亚基（CACNA1C）、胆碱能受体烟碱型α7亚基（CHRNA7）和丝裂原活化蛋白激酶1（MAPK1）。
选取242例患有MDD的韩国裔患者和326例健康对照作为分析样本。对CACNA1C、CHRNA7和MAPK1基因内的39个单核苷酸多态性（SNP）进行基因分型，随后检测其与MDD的关联性（主要分析）以及与其他临床特征（症状严重程度、发病年龄、自杀未遂史、治疗结果）的关联性（次要分析）。进行了单SNP、单倍型及上位性分析。
单SNP与疾病风险及临床特征无关。然而，发现MAPK1基因内的等位基因组合（单倍型）与MDD状态相关。次要分析检测到CACNA1C单倍型可能参与对抗抑郁治疗的抵抗。
这些数据分别提示MAPK1和CACNA1C在MDD风险及治疗抵抗中发挥作用。然而，由于分析存在诸多局限性，结果必须谨慎考虑并加以验证。
