title: Tumor necrosis factor-α and interleukin-6 expression in leukocytes and their association with polymorphisms and bone markers in diabetic individuals treated with pioglitazone.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of São Paulo, Sao Paulo, Brazil. sthimelfarb@usp.br
authors.forename: Silvia T
authors.initials: ST
authors.lastname: Himelfarb
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Silva
authors.forename: Simone S
authors.initials: SS
authors.lastname: Arazi
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Farjado
authors.forename: Adriana
authors.initials: A
authors.lastname: Garofalo
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Bertolami
authors.forename: Adriana
authors.initials: A
authors.lastname: Bertolami
authors.forename: Andre
authors.initials: A
authors.lastname: Faludi
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Sampaio
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Rezende
authors.forename: Rosario D C
authors.initials: RD
authors.lastname: Hirata
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; D015850:Interleukin-6; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase; D000077205:Pioglitazone