Tumor necrosis factor-α and interleukin-6 expression in leukocytes and their association with polymorphisms and bone markers in diabetic individuals treated with pioglitazone

摘要

Background: Pioglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) activator used in the treatment of type 2 diabetes (DM2) patients and it has been suggested that can induce bone loss. Tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) mRNA expression in blood leukocytes and the relationship with polymorphisms and bone markers in DM2 treated with pioglitazone were investigated. Methods: DM2 (n=53) and normoglycemic (NG, n=52) individuals were included. DM2 patients were treated with pioglitazone (45 mg/day/16 weeks). mRNA expression was evaluated by real-time polymerase chain reaction (PCR). TNFA-308G>A and IL6-174G>C polymorphisms were detected by PCR-RFLP and high resolution melting polymerase chain reaction (HRM-PCR). Results: Pioglitazone reduced bone specific alkaline phosphatase (bALP) and increased TNFα in DM2 group (p<0.001). DM2 or pioglitazone did not influence TNFα and IL-6 expression (p>0.05). TNFA-308A allele was associated with reduced basal TNFα mRNA levels in NG and DM2 and reduced alkaline phosphatase (tALP) after treatment (p<0.05). IL6-174C allele was associated with decreased oral glucose tolerance test (OGTT)-2 h in DM2 individuals (p<0.05). Conclusions: TNFA-308G >A polymorphism appear to be involved in regulation of gene expression independently of hyperglycemia and its interaction with pioglitazone may modify tALP, a important bone marker. IL6-174G>C variant is related with reduced risk of postprandial hyperglycemia but not with mRNA expression or bone markers.