RESUMO
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.
Assuntos
Aorta Torácica/patologia , Dissecção Aórtica/genética , Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Metaloproteinase 8 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Dissecção Aórtica/enzimologia , Aorta Torácica/enzimologia , Western Blotting , Estudos de Casos e Controles , Demografia , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the relevant expression of CXCL5 and CXCR2 in human atherosclerotic coronary artery and to study the association between the CXCL5 variant and coronary artery disease (CAD) in a Chinese Han population. MATERIALS AND METHODS: CXCL5 and CXCR2 expression in human coronary arteries was detected by immunohistochemical staining and western blotting analysis. The association between the CXCL5 variant and CAD was determined in a community-based sample by PCR-direct sequence analysis in a Chinese Han population. Finally, plasma CXCL5 levels were measured in a case-control study of CAD patients. RESULTS: We found that CXCL5 and CXCR2 expressions were higher in atherosclerotic coronary arteries plaque than in the normal coronary arteries. CXCL5 and CXCR2 expression levels increased in line with coronary artery lesion stages. A functional nonsynonymous -156 G/C in the CXCL5 promoter region was associated with CAD and plasma CXCL5 levels were significantly increased in CAD patients compared with control subjects (3891.21±1403.08 vs. 2812.39±840.62 pg/ml, P<0.05). Individuals with the CXCL5 promoter -156 G/C variant C/C and G/C carriers had higher plasma CXCL5 levels than those with the G/G genotype carriers in both CAD patients and control participants. CONCLUSION: CXCL5 and CXCR2 are enriched in human atherosclerotic coronary artery. Our findings show that the CXCL5 variant might be a genetic risk factor for the susceptibility of CAD and the CXCL5 promoter -156 G/C C allele might be an independent predictor for CAD. CXCL5 may be a useful molecular marker and a possible target for the treatment of CAD.