Clin Psychopharmacol Neurosci.  2019 Aug;17(3):364-368. 10.9758/cpn.2019.17.3.364.

Genes Involved in Neurodevelopment, Neuroplasticity and Major Depression: No Association for CACNA1C, CHRNA7 and MAPK1

Affiliations
  • 1Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
  • 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
  • 3Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea. pae@catholic.ac.kr
  • 4Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA.
  • 5Academic Medicine Education Institute, Duke-NUS Medical School, Singapore, Singapore.
  • 6Global Medical Education, New York, NY, USA.
  • 7Department of Psychiatry, Korea University College of Medicine, Seoul, Korea.
  • 8Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

OBJECTIVE: 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).
METHODS
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.
RESULTS
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.
CONCLUSION
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.

Keyword

MAPK1; CACNA1C; CHRNA7; Major depressive disorder; Deep phenotyping
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