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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376725" target="_blank" >RIV/00216208:11110/18:10376725 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/18:10376725

Výsledek na webu

<a href="https://doi.org/10.12659/MSM.907202" target="_blank" >https://doi.org/10.12659/MSM.907202</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.12659/MSM.907202" target="_blank" >10.12659/MSM.907202</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Background: Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer&apos;s disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and highrisk 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 epsilon 4 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 e4 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 epsilon 4 allele.

Název v anglickém jazyce

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

Popis výsledku anglicky

Background: Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer&apos;s disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and highrisk 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 epsilon 4 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 e4 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 epsilon 4 allele.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30215 - Psychiatry

Projekt

<a href="/cs/project/GA17-05292S" target="_blank" >GA17-05292S: Nové krevní biomarkery pro včasnou diagnostiku, prognózu a průběh Alzheimerovy nemoci</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Medical Science Monitor [online]

ISSN

1643-3750

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

2599-2619

Kód UT WoS článku

000431079300001

EID výsledku v databázi Scopus

2-s2.0-85046645012