Cited by 21Genetic Associations and EpidemiologyAlzheimer's disease research and treatmentsNeurotransmitter Receptor Influence on Behavior

Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder

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Kitzlerová, Eva, Fišar, Zdeněk, Lelková, Petra, Jirák, Roman, Zvěřová, Martina, Hroudová, Jana, Manukyan, Ada, Martásek, Pavel +1 more·2018·Medical Science Monitor

Abstract

BACKGROUND Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer's disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and high-risk groups. We tested for the contribution of interactions between multiple functional polymorphisms in the risk of MDD or AD. MATERIAL AND METHODS A genetic association case-control study was performed in 68 MDD cases, 84 AD cases (35 of them with comorbid depression), and 90 controls. The contribution of 7 polymorphisms from 5 genes (APOE, HSPA1A, SLC6A4, HTR2A, and BDNF) related to risk of MDD or AD development was analyzed. RESULTS Significant associations were found between MDD and interactions among polymorphisms in HSPA1A, SLC6A4, and BDNF or HSPA1A, BDNF, and APOE genes. For polymorphisms in the APOE gene in AD, significant differences were confirmed on the distributions of alleles and genotype rates compared to the control or MDD. Increased probability of comorbid depression was found in patients with AD who do not carry the ε4 allele of APOE. CONCLUSIONS Assessment of the interactions among polymorphisms of susceptibility loci in both MDD and AD confirmed a synergistic effect of genetic factors influencing inflammatory, serotonergic, and neurotrophic pathways at these heterogenous complex diseases. The effect of interactions was greater in MDD than in AD. A presence of the ε4 allele was confirmed as a genetic susceptibility factor in AD. Our findings indicate a role of APOE genotype in onset of comorbid depression in a subgroup of patients with AD who are not carriers of the APOE ε4 allele.

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  • Research has shown associations between depression and BDNF, candidate SNPs of the BDNF gene, polymorphisms of the BDNF gene, and the interaction of these polymorphisms with other determinants such as stress.

    “Research has shown associations between depression and BDNF (as well as candidate SNPs of the BDNF gene, polymorphisms of the BDNF gene, and the interaction of these polymorphisms with other determinants, such as stress) [129,144,145].”

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Research works printed but not linked: 1

  1. [32]Ye Q Bai F Zhang Z Shared genetic risk factors for late-life depression and Alzheimer’s disease J Alzheimers Dis 2016 52 1 15 27060956

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Authors
Kitzlerová, E., Fišar, Z., Lelková, P., Jirák, R., Zvěřová, M., Hroudová, J., Manukyan, A., Martásek, P., & Raboch, J.
Affiliations
  • Charles University (CZ)
  • Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Corresponding author
Fišar, Zdeněk
Venue
Medical Science Monitor
Published
2018-04-28
Volume
24
Pages
2599-2619
ISSN
  • 1234-1010 (ISSN-L)
  • 1643-3750
OpenAlex
W2802909891
Cited by
21
References
140
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 5
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Medical Science Monitor (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
Alzheimer's disease, major depressive disorder, genetic susceptibility loci, gene-gene interaction, polymorphism, APOE ε4, HSPA1A, serotonin transporter, HTR2A, brain-derived neurotrophic factor, comorbid depression, serotonergic pathways, inflammatory signaling
MeSH terms
Aged, Alleles, Alzheimer Disease, Demography, Depressive Disorder, Major, Major Depressive Disorder, Epistasis, Genetic, Female, Gene Frequency, Humans, Male, Middle Aged, Polymorphism, Genetic, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Loci, Genetic Association Studies

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