2018
CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population
HÁLOVÁ, Alice, Jana JANOUTOVA, Laura EWERLINGOVÁ, Vladimír JANOUT, Ondřej BONCZEK et. al.Základní údaje
Originální název
CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population
Autoři
HÁLOVÁ, Alice (203 Česká republika, domácí), Jana JANOUTOVA (203 Česká republika), Laura EWERLINGOVÁ (703 Slovensko, domácí), Vladimír JANOUT (203 Česká republika), Ondřej BONCZEK (203 Česká republika, domácí), Tomáš ZEMAN (203 Česká republika, domácí), Tereza GERGURI (203 Česká republika), Vladimír Josef BALCAR (36 Austrálie) a Omar ŠERÝ (203 Česká republika, garant, domácí)
Vydání
Journal of Biomedical Science, BioMed website, BioMed Central, London, England, 2018, 1021-7770
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 5.203
Kód RIV
RIV/00216224:14310/18:00103243
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000432822700001
Klíčová slova anglicky
Alzheimer's disease; Polymorphism; Gene; Association; Choline acetyltransferase
Změněno: 23. 4. 2024 11:23, Mgr. Michal Petr
Anotace
V originále
Background: 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 before. Methods: 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. Results: The 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. Conclusions: 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.
Návaznosti
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