CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F18%3A00494766" target="_blank" >RIV/67985904:_____/18:00494766 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/18:00103243 RIV/61988987:17110/18:A20020Q7

Result on the web

<a href="http://dx.doi.org/10.1186/s12929-018-0444-2" target="_blank" >http://dx.doi.org/10.1186/s12929-018-0444-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12929-018-0444-2" target="_blank" >10.1186/s12929-018-0444-2</a>

Result language

angličtina

Original language name

CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population

Original language description

Cholinergic hypothesis of Alzheimer's disease (AD) is based on the findings that a reduced and/or perturbed cholinergic activity in the central nervous system correlates with cognitive decline in patients with Alzheimer's disease. The hypothesis resulted in the development of centrally-acting agents potentiating cholinergic neurotransmission, these drugs, however, only slowed down the cognitive decline and could not prevent it Consequently, the perturbation of the central cholinergic signalling has been accepted as a part of the Alzheimer's aetiology but not necessarily the primary cause of the disease. In the present study we have focused on the rs3810950 polymorphism of ChAT (choline acetyltransferase) gene that has not been studied in Czech population befor.We carried out an association study to test for a relationship between the rs3810950 polymorphism arid Alzheimer's disease in a group of 1186 persons, 759 patients with Alzheimer's disease and 427 control subjects. Furthermore, we performed molecular modelling of the terminal domain (1st-126th amino acid residue) of one of the ChAT isoforms (M) to visualise in silico whether the rs3810950 polymorphism (A120T) can change any features of the tertiary structure of the protein which would have a potential to alter its function. nThe AA genotype of CHAT was associated with a 1.25 times higher risk of AD (p < 0.002) thus demonstrating that the rs3810950 polymorphism can have a modest but statistically significant effect on the risk of AD in the Czech population. Furthermore, the molecular modelling indicated that the polymorphism is likely to be associated with significant variations in the tertiary structure of the protein molecule which may impact its enzyme activity. Our findings are consistent with the results of the meta-analytical studies of the relationship between rs3810950 polymorphism and AD and provide further material evidence for a direct (primary) involvement of cholinergic mechanisms in the etiopathogenesis of AD, particularly as a factor in cognitive decline and perturbed conscious awareness commonly observed in patients with AD.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/NV16-31207A" target="_blank" >NV16-31207A: Genetics and Epidemiology of Alzheimer´s disease</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Journal of Biomedical Science

ISSN

1021-7770

e-ISSN

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Volume of the periodical

25

Issue of the periodical within the volume

1

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

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UT code for WoS article

000432822700001

EID of the result in the Scopus database

2-s2.0-85047014440