Associação entre o polimorfismo – 137G/C no gene da interleucina-18 e o perfil clínico e laboratorial de pacientes com diabetes mellitus tipo 2

Abstract

nterleukin-18 (IL-18), a pro-inflammatory and proatherogenic cytokine, has been associated with diabetes type 2 (DM2), metabolic syndrome, stroke and cardiovascular disease (CVD). Some studies have indicated that the IL-18 -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of DM2 and its complications. The aim of the present study was to evaluate whether the -137G / C polymorphism is associated with the occurrence of T2DM, IL-18 levels, cardiovascular risk markers, and clinical manifestations in Brazilian T2DM patients.The study was approved by the Ethics Committee (No. 3,048,186) and conducted with 226 patients, 125 T2DM patients in follow-up in a reference endocrinology service and 101 control individuals with no history of diabetes.The –137G/C polymorphism in IL-18 gene and serum IL-18 levels were determined using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay, respectively. Higher levels of IL-18 were found in the group of diabetic patients compared to control subjects (305,2 pg/mL e 191,6 pg/mL, respectively). The mean values of glucose and triglycerides were significantly higher in the group of diabetic patients (159,7 mg/dL e 175,8 mg/dL,respectively). In opposition, mean values of total cholesterol, HDL-c and LDL-c were higher in the control group (193,7 mg/dL, 51,2 mg/dL e 114,2 mg/dL, respectively). We found an association between the CC genotype and CVD and diabetic nephropathyin T2DM patients, as well as serum levels of IL-18 were higher in CC carriers (843,1 pg/mL) compared with GG or GC carriers (303,6 pg/mL e 292 pg/mL, respectively).Additionally, the present study shows that CC genotype had higher concentrations of the creatinine and albuminuria compared with the GG or GC genotypes. Patients with CVD and T2DM had higher glucose, glycated hemoglobin, serum creatinine, microalbuminuria, serum IL-18, and visceral fat values compared to DM2 patients without CVD. The results suggest that the CC genotype is associated with the development of CVD and diabetic nephropathy, suggesting that the -137 G/C polymorphism typing in DM2 patients may represent an important tool in reducing CVD morbidity and mortality.