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Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

Wang XZ, Du XM, Jing QM, Li XX, Gu RX, Wang J, Han YL - Mol. Biol. Rep. (2013)

Bottom Line: Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD.The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD.TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Cardiovascular Research Institute, Northern Hospital, 83 Wenhua Road, Shenyang, 110840, Liaoning, China.

ABSTRACT
The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.

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Western blot and ELISA Analyses for MMP8 in control and TAD subjects. Plasma MMP8 levels in TAD patients and control subjects by ELISA (a); Plasma MMP8 levels in subgroup subjects according to MMP8 -C799T genotype (b); MMP8 protein concentration in the TAD wall of patients having either the TT, CT or CC genotypes (c).The difference between groups was analyzed by one-way ANOVA tests
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Fig1: Western blot and ELISA Analyses for MMP8 in control and TAD subjects. Plasma MMP8 levels in TAD patients and control subjects by ELISA (a); Plasma MMP8 levels in subgroup subjects according to MMP8 -C799T genotype (b); MMP8 protein concentration in the TAD wall of patients having either the TT, CT or CC genotypes (c).The difference between groups was analyzed by one-way ANOVA tests

Mentions: Figure 1a shows the effect of the MMP8 C-799T polymorphism on MMP8 activity in controls and TAD patients. There was a significant difference in plasma MMP8 levels among 3 genotypes of C-799T in the control and TAD groups (P < 0.05). MMP8 activity in TAD patients ranged from 13.90 to 22.69 μg/L, and from 8.16 to 18.73 μg/L in controls. We found that the MMP8 level was significantly higher in subjects with the TT genotype (19.01 ± 2.50 μg/L) than those with CT (17.66 ± 1.92 μg/L) and CC (16.14 ± 2.26 μg/L) genotypes in the TAD group (P < 0.05) (Fig. 1b). Western blotting analysis showed that significantly greater amounts of MMP8 protein were present in the thoracic aorta wall of MMP8 799TT homozygotes, than in MMP8 C-799T heterozygotes and MMP8 799CC homozygotes (Fig. 1c).Fig. 1


Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

Wang XZ, Du XM, Jing QM, Li XX, Gu RX, Wang J, Han YL - Mol. Biol. Rep. (2013)

Western blot and ELISA Analyses for MMP8 in control and TAD subjects. Plasma MMP8 levels in TAD patients and control subjects by ELISA (a); Plasma MMP8 levels in subgroup subjects according to MMP8 -C799T genotype (b); MMP8 protein concentration in the TAD wall of patients having either the TT, CT or CC genotypes (c).The difference between groups was analyzed by one-way ANOVA tests
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824396&req=5

Fig1: Western blot and ELISA Analyses for MMP8 in control and TAD subjects. Plasma MMP8 levels in TAD patients and control subjects by ELISA (a); Plasma MMP8 levels in subgroup subjects according to MMP8 -C799T genotype (b); MMP8 protein concentration in the TAD wall of patients having either the TT, CT or CC genotypes (c).The difference between groups was analyzed by one-way ANOVA tests
Mentions: Figure 1a shows the effect of the MMP8 C-799T polymorphism on MMP8 activity in controls and TAD patients. There was a significant difference in plasma MMP8 levels among 3 genotypes of C-799T in the control and TAD groups (P < 0.05). MMP8 activity in TAD patients ranged from 13.90 to 22.69 μg/L, and from 8.16 to 18.73 μg/L in controls. We found that the MMP8 level was significantly higher in subjects with the TT genotype (19.01 ± 2.50 μg/L) than those with CT (17.66 ± 1.92 μg/L) and CC (16.14 ± 2.26 μg/L) genotypes in the TAD group (P < 0.05) (Fig. 1b). Western blotting analysis showed that significantly greater amounts of MMP8 protein were present in the thoracic aorta wall of MMP8 799TT homozygotes, than in MMP8 C-799T heterozygotes and MMP8 799CC homozygotes (Fig. 1c).Fig. 1

Bottom Line: Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD.The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD.TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Cardiovascular Research Institute, Northern Hospital, 83 Wenhua Road, Shenyang, 110840, Liaoning, China.

ABSTRACT
The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.

Show MeSH
Related in: MedlinePlus