Association between cystatin C gene polymorphism and the prevalence of white matter lesion in elderly healthy subjects.
Age of Onset
Aged
Aged, 80 and over
Alleles
Comorbidity
Cystatin C
/ genetics
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Leukoencephalopathies
/ diagnosis
Male
Middle Aged
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Prevalence
White Matter
/ pathology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
16
09
2019
accepted:
28
01
2020
entrez:
15
3
2020
pubmed:
15
3
2020
medline:
24
11
2020
Statut:
epublish
Résumé
Cystatin C (CST3) is a cysteine protease inhibitor abundant in the central nervous system, and demonstrated to have roles in several pathophysiological processes including vascular remodeling and inflammation. Previously, we showed a relation of CST3 gene polymorphisms with deep and subcortical white matter hyperintensity (DSWMH) in a small case-control study. In this study, we aimed to investigate the relation in a larger cross-sectional study. Participants of a brain health examination program were recruited (n = 1795) in the study, who underwent routine blood tests and cognitive function tests. Cerebral white matter changes were analyzed by MRI. Additionally, 7 single nucleotide polymorphisms (SNPs) (-82G/C, -78T/G, -5G/A, +4A/C, +87C/T, +148G/A and +213G/A) in the promoter and coding regions of CST3 gene were examined. Among them, carriers of the minor allele haplotype -82C/+4C/+148A were significantly associated with decreased CST3 concentration in the plasma. Unadjusted analysis did not show significant relation between carriers of the minor allele haplotype and periventricular hyperintensity (PVH), but DSWMH was marginally (p < 0.054) increased in this group. After adjusting the effects of other variables like age and kidney function, logistic regression analysis revealed that carriers of the minor allele haplotype were at a significantly increased risk of developing both PVH and DSWMH. Thus, our results suggest that carriers of the minor allele haplotype -82C/+4C/+148A of CST3 gene could be at an increased risk to develop cerebral white matter disturbance.
Identifiants
pubmed: 32170118
doi: 10.1038/s41598-020-61383-7
pii: 10.1038/s41598-020-61383-7
pmc: PMC7069982
doi:
Substances chimiques
Cystatin C
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4688Références
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