IVS1 -397T>C estrogen receptor α polymorphism is associated with low-grade systemic inflammatory response in type 1 diabetic girls.

Purpose: 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.