Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis

Djurić, Tamara; Živković, Maja; Radak, Djordje; Jekic, Djole; Radak, Sandra; Stojković, Ljiljana; Raicević, R; Stanković, Aleksandra; Alavantić, Dragan

doi:10.1016/j.clinbiochem.2008.08.081

Cited by 25 publications

(12 citation statements)

References 26 publications

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“…However, the same polymorphic variant can also exert deleterious effects. The lower tissue activity of MMP-3 in 6A/6A patients alters the remodeling process of ECM in the direction of facilitating the progress of atherosclerosis [29]. …”

Section: Discussionmentioning

confidence: 99%

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse

et al. 2012

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Introduction and hypothesisTo investigate the associations between single nucleotide polymorphism (SNP) type 1G/2G at position −1607/−1608 of the matrix metalloproteinase (MMP)-1 gene and SNP type 5A/6A at position −1612/-1617 of the MMP-3 gene and the development of pelvic organ prolapse (POP) in women.Methods133 patients with symptomatic POP were included in the study group. The control group consisted of 132 women with a normal pelvic floor. 1G/2G MMP-1 and 5A/6A MMP-3 SNPs were determined by polymerase chain reaction (PCR) and restriction fragments length polymorphism analysis.ResultsWhen estimated individually none of the investigated SNPs were associated with POP. The combined MMP-1/MMP-3 SNP analysis showed that the following polymorphic pairs were overrepresented in women with POP: 1G/2G −5A/6A, 2G/2G −5A/6A, 2G/2G −5A/5A, 1G/1G −6A/6A, p = 0.005.ConclusionsThe combined effect of −1607/−1608 MMP-1 and −1612/−1617 MMP-3 SNPs may contribute to the development of POP in some women.

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Section: Discussionmentioning

confidence: 99%

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse

et al. 2012

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“…The 5A allele, found to be associated with reduced risk of SIA in our study, has been shown to have increased promoter activity as compared to the 6A allele [Ye et al, 1996; Zhu et al, 2006]. In the context of adulthood diseases, the 5A allele has been linked to a number of cancers, such as lung cancer [Fang et al, 2005], oral cancer [Vairaktaris et al, 2007], and bladder cancer [Srivastava et al, 2010], while the 6A allele has been associated with increased risk of such conditions as carotid atherosclerosis [Djuric et al, 2008]. In the context of pediatric disease, MMP3 has been shown to have involvement in the intestine: it has been suggested that elevated expression of MMP3 may lead to injury of the intestine and inflammation as part of inflammatory bowel disease (reviewed by Louis et al [2000] and Naito and Yoshikawa [2005]).…”

Section: Discussionmentioning

confidence: 99%

Considering the vascular hypothesis for the pathogenesis of small intestinal atresia: A case control study of genetic factors

Gupta

Yang

Iovannisci³

et al. 2013

American J of Med Genetics Pt A

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Small intestinal atresia (SIA) is a rare congenital occlusion of the small intestine. SIA development, particularly in the jejunum and ileum, has been associated with in utero disruption of vascular supply. However, the number of studies of the vascular hypothesis is limited. This study considers the vascular hypothesis by exploring risks associated with 32 SNPs of genes involved in vascular processes of homocysteine metabolism, coagulation, cell-cell interactions, inflammatory response, and blood pressure regulation. A total of 206 SIA cases were ascertained by the California Birth Defects Monitoring Program, and 573 infants with no major congenital anomalies by their first birthday were selected as controls. Genomic DNA was genotyped for 32 SNPs involving the following genes: MTHFR, F2, F5, F7, SERPINE1, FGB, ITGA2, ITGB3, SELE, ICAM1, MMP3, TNF, LTA, NOS3, AGTR1, AGT, NPPA, ADD1, SCNN1A, GNB3, and ADRB2. Risks were estimated as odds ratios, adjusted for maternal age and race, with 95% confidence intervals. Cases were considered collectively and by subgroups based on atresia location (duodenal/jejunum/ileum). Three SNPs had reduced risk: SERPINE1 11053 T/G, MMP3 (-1171) A6/A5, and ADRB2 gln27glu. Two had increased risk: ITGA2 873 G/A and NPPA 2238 T/C. No intestinal subphenotypes showed a unique pattern of SNP associations. The association of two SNPs with increased risk lends some, albeit limited, support to vascular impairment as a possible mechanism leading to SIA. These results also identify genes meriting further exploration in SIA studies. Hence, this study makes an important contribution by exploring the long-held but not well-investigated vascular hypothesis.

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“…Current evidence suggests that MMPs play a role in early atherosclerosis, plaque rupture, and MI. Some studies have shown the associations between the low-activity 6A allele and both coronary and carotid atherosclerosis, and increased intima-media thickness (33-35). This suggests that individuals with the 6A/6A genotype, which leads to the lower production of MMP-3, have an altered matrix turnover favoring the deposition of matrix and accelerated atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Does Matrix Metalloproteinase-3 Polymorphism Play a Role in Age-Related Macular Degeneration in Patients With Myocardial Infarction?

Liutkevičienė

Žaliaduonytė-Pekšienė

Žaliūnienė

et al. 2012

Medicina

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Summary Objective The aim of our study was to determine if the genotype of the matrix metalloproteinase-3 (MMP-3) gene might carry the risk of age-related macular degeneration (ARMD) in patients with myocardial infarction. Material and Methods A total of 499 patients with an acute myocardial infarction or with a history of myocardial infarction were enrolled into the study. They were subdivided into 2 groups: 273 patients with ARMD and 226 patients without ARMD. The control group comprised 560 persons from a random sample of the Lithuanian population. DNA was analyzed using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position −1171 of the MMP-3 gene promoter. Results Of the 499 patients with myocardial infarction, 47% had early-stage ARMD. The patients with ARMD were older than the patients in the group without ARMD (62.1±10.8 vs. 59.6±11.1, P<0.01). The analysis of MMP-3 gene polymorphism did not reveal any differences in the distribution of 5A/5A, 5A/6A, and 6A/6A genotypes between the ARMD group, non-ARMD group, and the control group (24.2%, 52.5%, and 23.3% in the ARMD group; 28.7%, 51.9%, and 19.4% in non-ARMD group; and 25.7%, 49.3% and 25.0%, in the control group, respectively). Conclusions MMP-3 gene polymorphism had no predominant effect on the development of ARMD in patients with myocardial infarction.

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Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis

Cited by 25 publications

References 26 publications

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse

Considering the vascular hypothesis for the pathogenesis of small intestinal atresia: A case control study of genetic factors

Does Matrix Metalloproteinase-3 Polymorphism Play a Role in Age-Related Macular Degeneration in Patients With Myocardial Infarction?

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