Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study
Nema prikaza
Autori
Đurić, TamaraStanković, Aleksandra
Končar, Igor
Radak, Đorđe J.
Davidović, Lazar
Alavantić, Dragan
Živković, Maja
Članak u časopisu
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Objective: Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799 C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue. Methods: The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR. Results: In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR,... 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; SE. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003). Conclusion: Our preliminary results indicate that MMP-8 -381A/G and -799 C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Ključne reči:
MMP-8 / Gene polymorphism / Haplotype / Gene expression / Carotid atherosclerosisIzvor:
Atherosclerosis, 2011, 219, 2, 673-678Finansiranje / projekti:
- Genetska osnova humanih vaskularnih i inflamatornih bolesti (RS-MESTD-Basic Research (BR or ON)-175085)
- Integralna studija identifikacije regionalnih genetskih faktora rizika i faktora rizika životne sredine za masovne nezarazne bolesti humane populacije u Srbiji - INGEMA_S (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41028)
DOI: 10.1016/j.atherosclerosis.2011.08.025
ISSN: 0021-9150
PubMed: 21906737
WoS: 000298813900048
Scopus: 2-s2.0-82955194840
Kolekcije
Institucija/grupa
VinčaTY - JOUR AU - Đurić, Tamara AU - Stanković, Aleksandra AU - Končar, Igor AU - Radak, Đorđe J. AU - Davidović, Lazar AU - Alavantić, Dragan AU - Živković, Maja PY - 2011 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4641 AB - Objective: Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799 C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue. Methods: The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR. Results: In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; SE. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003). Conclusion: Our preliminary results indicate that MMP-8 -381A/G and -799 C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved. T2 - Atherosclerosis T1 - Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study VL - 219 IS - 2 SP - 673 EP - 678 DO - 10.1016/j.atherosclerosis.2011.08.025 ER -
@article{ author = "Đurić, Tamara and Stanković, Aleksandra and Končar, Igor and Radak, Đorđe J. and Davidović, Lazar and Alavantić, Dragan and Živković, Maja", year = "2011", abstract = "Objective: Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799 C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue. Methods: The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR. Results: In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; SE. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003). Conclusion: Our preliminary results indicate that MMP-8 -381A/G and -799 C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.", journal = "Atherosclerosis", title = "Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study", volume = "219", number = "2", pages = "673-678", doi = "10.1016/j.atherosclerosis.2011.08.025" }
Đurić, T., Stanković, A., Končar, I., Radak, Đ. J., Davidović, L., Alavantić, D.,& Živković, M.. (2011). Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study. in Atherosclerosis, 219(2), 673-678. https://doi.org/10.1016/j.atherosclerosis.2011.08.025
Đurić T, Stanković A, Končar I, Radak ĐJ, Davidović L, Alavantić D, Živković M. Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study. in Atherosclerosis. 2011;219(2):673-678. doi:10.1016/j.atherosclerosis.2011.08.025 .
Đurić, Tamara, Stanković, Aleksandra, Končar, Igor, Radak, Đorđe J., Davidović, Lazar, Alavantić, Dragan, Živković, Maja, "Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study" in Atherosclerosis, 219, no. 2 (2011):673-678, https://doi.org/10.1016/j.atherosclerosis.2011.08.025 . .