RESUMEN
Background: Type 2 diabetes mellitus (T2DM) is an inflammatory condition associated to obesity and increased oxidative stress. Haptoglobin (Hp) is an acute phase reactant that scavenges extracorpuscular hemoglobin from circulation and prevents heme-iron oxidative damage. Objective: To assess the association between Hp levels and Hp1-Hp2 gene polymorphism and clinical and laboratory parameters in patients with T2DM. Methods: The study sample consisted of 102 T2DM patients and 62 controls. Hp plasma levels were measured using an ELISA assay, and Hp genotyping was performed using a specific two-step allelic polymerase chain reaction. Results: Hp levels were higher in T2DM patients as compared to controls (p=0.005). T2DM patients with high blood pressure had higher Hp levels than patients without this comorbidity (p=0.021). Obese T2DM patients had higher Hp levels as compared to obese controls (p=0.009) and to non-obese T2DM patients (p=0.003). The Hp1-Hp1 genotype was showed to be associated to T2DM according to additive (OR=3.038, 95% CI 1.127-8.192; p=0.036) and dominant model (OR=0.320, 95% CI 0.118-0.839; p=0.010), but Hp2 allele carriers contributed with higher Hp levels in T2DM as compared to controls. Waist circumference (p=0.002), BMI (p=0.001), and IL-6 (p=0.012), and hs-CRP (p=0.001) levels positively correlated with Hp levels in the T2DM group. Conclusion: These results suggest that Hp levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammatory status, and high blood pressure in T2DM
Antecedentes: La diabetes mellitus tipo 2 (DM2) es una afección inflamatoria asociada con la obesidad y el aumento del estrés oxidativo. La haptoglobina (Hp) es un reactante de fase aguda que elimina la hemoglobina extracorpuscular de la circulación y previene el daño oxidativo del hierro hemo. Objetivo: Evaluar la asociación entre los niveles de Hp y el polimorfismo del gen Hp1-Hp2, y los parámetros clínicos y de laboratorio en individuos con DM2. Métodos: Ciento dos pacientes con DM2 y 62 controles se incluyeron en este estudio. Los niveles plasmáticos de Hp se cuantificaron por ELISA y el genotipado de Hp se llevó a cabo mediante una PCR alelo-específica en dos pasos. Resultados: Los niveles de Hp fueron más altos en pacientes con DM2 en comparación con los controles (p=0,005). Los pacientes con DM2 con hipertensión arterial mostraron niveles más altos de Hp en comparación con los pacientes sin hipertensión (p=0,021). Los pacientes obesos con DM2 mostraron niveles más altos de Hp en comparación con los controles obesos (p=0,009) y con los pacientes con DM2 no obesos (p=0,003). El genotipo Hp1-Hp1 mostró asociación con DM2 según el modelo aditivo (OR=3,038; IC 95%: 1,127-8,192; p=0,036) y el modelo dominante (OR=0,320; IC 95%: 0,118-0,839; p=0,010), pero entre los portadores del alelo Hp2, las concentraciones de Hp eran más altas en T2DM que en controles. La circunferencia de la cintura (p=0,002), el IMC (p=0,001), IL-6 (p=0,012) y la hs-CRP (p=0,001) se correlacionaron positivamente con los niveles de Hp en el grupo DM2. Conclusión: Estos resultados sugieren que los niveles de Hp están influenciados por el polimorfismo Hp1-Hp2, la obesidad, el estado inflamatorio y la hipertensión en DM2
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Haptoglobinas/fisiología , Polimorfismo Genético/genética , Haptoglobinas/análisis , Haptoglobinas/genética , Polimorfismo Genético/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Inflamación/fisiopatología , Hipertensión/fisiopatología , Obesidad/fisiopatología , Brasil , Estudios de Casos y Controles , Estudios Transversales , Genoma Humano/fisiologíaRESUMEN
ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.