RESUMEN
Background: Matrix metalloproteinase (MMP) enzyme gene polymorphisms MMP-2-1575G/A and MMP-9-1562C/T promoter polymorphism, their serum levels, and activity are associated with aortic valve calcification (AVC). Materials and Methods: The synergistic link between the risk of AVC and the alleles T and A of MMP-9 and MMP-2 was investigated, respectively. Ninety-two cases with AVC and 92 healthy individuals from the west of Iran were included, and MMP- 2-1575G/A and MMP-9-1562C/T promoter polymorphisms were detected using PCR-RFLP. The serum levels and activity of MMP-2 and -9 were assessed using ELISA and gelatin zymography methods, respectively. In addition, serum biochemical markers, including FBS, urea and creatinine, cholesterol, triglyceride, HDL, LDL, calcium, phosphorus, and blood pressure: systolic blood pressure and diastolic blood pressure were measured. Results: Heart valve calcification disease was associated with a comparatively higher frequency of the A allele of the MMP2-1575 variation (p = 0.002). In addition, the frequency of T allele of the MMP9-1562 variant was higher than the control group (p = 0.007). Conclusion: MMP-2 and MMP-9 serum levels and activities were observed to be considerably higher in the experimental group than in the control group (p < 0.001). Patients are more susceptible to cardiovascular disease than the control group due to elevated serum levels and activity of MMP-2 and MMP-9.
Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Predisposición Genética a la Enfermedad , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Regiones Promotoras Genéticas , Humanos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/sangre , Calcinosis/genética , Calcinosis/sangre , Femenino , Masculino , Irán , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/sangre , Válvula Aórtica/patología , Regiones Promotoras Genéticas/genética , Persona de Mediana Edad , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/sangre , Polimorfismo de Nucleótido Simple/genética , Anciano , Adulto , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/sangre , GenotipoRESUMEN
The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of coronary artery calcification (CAC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with CAC. One hundred and fifty-five cases with CAC and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR-RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS (fasting blood sugar), urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with CAC when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to CAC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in CAC cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Calcificación Vascular/genética , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Irán , Lípidos/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Regulación hacia Arriba , Calcificación Vascular/sangre , Calcificación Vascular/diagnósticoRESUMEN
Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.