RESUMO
AIMS: Cardiovascular diseases are the major cause of mortality in patients with diabetes mellitus. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in cardiovascular diseases. The objective of this study was to evaluate the relation between the genotypes of the MCP-1 A-2518G polymorphism and the development of carotid atherosclerosis in patients with type 2 diabetes. METHODS: The subjects were 303 unrelated patients who were diagnosed with type 2 diabetes mellitus. To evaluate macroangiopathy, we measured carotid artery intima-media thickness (IMT) by ultrasonography. The MCP-1 A-2518G polymorphism was determined by TaqMan PCR method. RESULTS: IMT in patients with the MCP-1 -2518 AG or GG genotype was significantly greater than the AA-genotype (P=0.007). Simple regression analysis showed that age, systolic blood pressure, LDL-cholesterol, the MCP-1 -2518 AG+GG polymorphism, and HbA1c level were correlated with IMT (P<0.0001, <0.0001, 0.006, 0.007, 0.025, respectively). In multiple regression analysis, the MCP-1 -2518 AG+GG polymorphism was the third strongest independent determinant of IMT in patients with type 2 diabetes (P=0.021), subsequent to age and systolic blood pressure. CONCLUSION: Assessment of the MCP-1 A-2518G polymorphism would be useful in identifying the risk of developing carotid atherosclerosis in patients with type 2 diabetes.
Assuntos
Doenças das Artérias Carótidas/genética , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Adenina , Idoso , Povo Asiático/genética , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/diagnóstico por imagem , Feminino , Genótipo , Humanos , Japão , Masculino , Reação em Cadeia da Polimerase/métodos , Análise de Regressão , Timina , UltrassonografiaRESUMO
OBJECTIVE: The development of diabetic nephropathy is considered to be associated with oxidative stress. NADPH oxidase and the receptor for advanced glycation end products (RAGE) have attracted attention as mechanisms of generating oxidative stress. We studied the relation between the genotypes of the NADPH p22phox C242T and RAGE G1704T polymorphisms and the development of diabetic nephropathy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Using a retrospective review of clinical data, we allocated 181 Japanese type 2 diabetic patients to one of two groups: patients without diabetic nephropathy (group N; n = 108) and patients developing diabetic nephropathy (group D; n = 73) for 10 years or more. The p22phox C242T and RAGE G1704T polymorphisms were examined by Taqman PCR methods. RESULTS: The frequency of the p22phox CC genotype was significantly higher in group D than in group N (90 vs. 79%; P = 0.0427). The frequency of the RAGE GT + TT genotype was significantly higher in group D than in group N (26 vs. 13%; P = 0.0313). The frequency of the combination of p22phox CC and RAGE GT + TT genotypes was significantly higher in group D than in group N (22 vs. 8%; P = 0.0057). In multiple logistic regression analysis, systolic blood pressure, HbA(1c), triglycerides, and the combination of polymorphisms were shown to be independent variables. CONCLUSIONS: These results suggest that assessment of the combination of NADPH p22phox C242T and RAGE G1704T polymorphisms may be useful in identifying the risk for developing diabetic nephropathy in type 2 diabetic patients.
