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Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder
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 multi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944403/ https://www.ncbi.nlm.nih.gov/pubmed/29703883 http://dx.doi.org/10.12659/MSM.907202 |
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author | Kitzlerová, Eva Fišar, Zdeněk Lelková, Petra Jirák, Roman Zvěřová, Martina Hroudová, Jana Manukyan, Ada Martásek, Pavel Raboch, Jiří |
author_facet | Kitzlerová, Eva Fišar, Zdeněk Lelková, Petra Jirák, Roman Zvěřová, Martina Hroudová, Jana Manukyan, Ada Martásek, Pavel Raboch, Jiří |
author_sort | Kitzlerová, Eva |
collection | PubMed |
description | 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/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 ɛ4 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 ɛ4 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 ɛ4 allele. |
format | Online Article Text |
id | pubmed-5944403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59444032018-05-11 Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder Kitzlerová, Eva Fišar, Zdeněk Lelková, Petra Jirák, Roman Zvěřová, Martina Hroudová, Jana Manukyan, Ada Martásek, Pavel Raboch, Jiří Med Sci Monit Lab/In Vitro Research 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/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 ɛ4 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 ɛ4 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 ɛ4 allele. International Scientific Literature, Inc. 2018-04-28 /pmc/articles/PMC5944403/ /pubmed/29703883 http://dx.doi.org/10.12659/MSM.907202 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Lab/In Vitro Research Kitzlerová, Eva Fišar, Zdeněk Lelková, Petra Jirák, Roman Zvěřová, Martina Hroudová, Jana Manukyan, Ada Martásek, Pavel Raboch, Jiří Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title | Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title_full | Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title_fullStr | Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title_full_unstemmed | Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title_short | Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder |
title_sort | interactions among polymorphisms of susceptibility loci for alzheimer’s disease or depressive disorder |
topic | Lab/In Vitro Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944403/ https://www.ncbi.nlm.nih.gov/pubmed/29703883 http://dx.doi.org/10.12659/MSM.907202 |
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