PHACTR1 haplotypes are associated with carotid plaque presence and affect PHACTR1 mRNA expression in carotid plaque tissue.
Adult
Aged
Carotid Artery Diseases
/ genetics
Case-Control Studies
Endarterectomy, Carotid
Female
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Introns
Male
Microfilament Proteins
/ genetics
Middle Aged
Plaque, Atherosclerotic
/ genetics
Polymorphism, Single Nucleotide
Up-Regulation
Atherosclerosis
Carotid plaque
Haplotype
PHACTR1
mRNA expression
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
20 Aug 2019
20 Aug 2019
Historique:
received:
07
02
2019
revised:
25
04
2019
accepted:
10
06
2019
pubmed:
15
6
2019
medline:
23
7
2019
entrez:
15
6
2019
Statut:
ppublish
Résumé
Carotid plaque is a hallmark of advanced carotid atherosclerosis and there is evidence of phosphatase and actin regulator 1 (PHACTR1) involvement in the processes that lead to atherosclerosis. PHACTR1 intronic variants have been associated with coronary artery disease and carotid dissection. Up to date the PHACTR1 haplotypes were not investigated in association with carotid plaque presence (CPP). So, the aims of this study were to investigate possible association of PHACTR1 haplotypes inferred from the intronic variants rs9349379, rs2026458 and rs2876300 with CPP in patients with advanced carotid atherosclerosis and to analyze their possible effect on PHACTR1 relative mRNA expression in carotid plaque tissue specimens. The study group consisted of 501 patients with evidence of carotid plaque presence admitted for carotid endarterectomy and 310 healthy controls. PHACTR1 rs9349379, rs2026458, rs2876300 and relative mRNA expression were detected by TaqMan® technology. We have found significant and independent association of haplotype ACA with the CPP, compared to the referent haplotype GTA (adjusted OR = 1.54 95% CI = 1.07-2.21, p = 0.02). The OR was adjusted for gender, age, BMI, hypertension and total cholesterol. The relative expression of PHACTR1 mRNA in carotid plaque tissue proved to be significantly higher in carriers of the ACG haplotype compared to the referent haplotype GTA (p = 0.03). Our results suggest that PHACTR1 haplotypes inferred from the variants rs9349379, rs2026458 and rs2876300 affect PHACTR1 mRNA and bear the risk for CPP in patients with advanced carotid atherosclerosis. Further replication and validation studies are inevitable.
Sections du résumé
BACKGROUND
BACKGROUND
Carotid plaque is a hallmark of advanced carotid atherosclerosis and there is evidence of phosphatase and actin regulator 1 (PHACTR1) involvement in the processes that lead to atherosclerosis. PHACTR1 intronic variants have been associated with coronary artery disease and carotid dissection. Up to date the PHACTR1 haplotypes were not investigated in association with carotid plaque presence (CPP). So, the aims of this study were to investigate possible association of PHACTR1 haplotypes inferred from the intronic variants rs9349379, rs2026458 and rs2876300 with CPP in patients with advanced carotid atherosclerosis and to analyze their possible effect on PHACTR1 relative mRNA expression in carotid plaque tissue specimens.
METHODS
METHODS
The study group consisted of 501 patients with evidence of carotid plaque presence admitted for carotid endarterectomy and 310 healthy controls. PHACTR1 rs9349379, rs2026458, rs2876300 and relative mRNA expression were detected by TaqMan® technology.
RESULTS
RESULTS
We have found significant and independent association of haplotype ACA with the CPP, compared to the referent haplotype GTA (adjusted OR = 1.54 95% CI = 1.07-2.21, p = 0.02). The OR was adjusted for gender, age, BMI, hypertension and total cholesterol. The relative expression of PHACTR1 mRNA in carotid plaque tissue proved to be significantly higher in carriers of the ACG haplotype compared to the referent haplotype GTA (p = 0.03).
CONCLUSION
CONCLUSIONS
Our results suggest that PHACTR1 haplotypes inferred from the variants rs9349379, rs2026458 and rs2876300 affect PHACTR1 mRNA and bear the risk for CPP in patients with advanced carotid atherosclerosis. Further replication and validation studies are inevitable.
Identifiants
pubmed: 31200082
pii: S0378-1119(19)30580-3
doi: 10.1016/j.gene.2019.06.020
pii:
doi:
Substances chimiques
Microfilament Proteins
0
PHACTR1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-278Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.