title: IVS1 -397T>C estrogen receptor α polymorphism is associated with low-grade systemic inflammatory response in type 1 diabetic girls.
abstract: OBJECTIVE
  The study aimed to investigate the influence of estrogen receptor α (ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes.
  
  
  METHODS
  152 young regularly menstruating girls with diagnosed type 1 diabetes and 84 young, healthy menstruating girls were recruited. ER-α genotyping was carried out by PCR. Serum concentrations of 17β-estradiol, as well as IL-6, TNF-α, VEGF, and IL-10, were measured. CD4(+)Foxp3(+) TH17 cells were isolated and analyzed by flow cytometry.
  
  
  RESULTS
  Type 1 diabetic girls carrying TT genotype were characterized by the lowest serum estradiol level and IL-10 and highest IL-6, TNF-α, and VEGF. The association between the level of certain cytokine and the genetic variant of estrogen receptor α polymorphism was analyzed. Frequencies of CD4(+)Foxp3(+) TH17 cells were also enhanced in TT bearing girls with type 1 diabetes and correlated with the level of analyzed cytokines. In addition, the correlation between serum estradiol level and cytokine concentrations was observed.
  
  
  CONCLUSIONS
  We propose that TT variant of estrogen receptor α polymorphism may be associated with enhanced inflammatory response, which in turn may lead to acceleration of diabetic retino- and nephropathy in girls with type 1 diabetes. This finding may help the physicians to predict the onset and progression of diabetic microvascular complications.
authors: Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.
authors: Monika
authors: M
authors: Ryba-Stanisławowska
authors: Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.
authors: Karolina
authors: K
authors: Rybarczyk-Kapturska
authors: Clinic of Pediatrics, Department of Diabetology and Endocrinology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
authors: Agnieszka
authors: A
authors: Brandt
authors: Clinic of Pediatrics, Department of Diabetology and Endocrinology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
authors: Małgorzata
authors: M
authors: Myśliwiec
authors: Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.
authors: Jolanta
authors: J
authors: Myśliwska
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008833:Microcirculation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D058504:Th17 Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016207:Cytokines; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D004958:Estradiol