%0 Journal Article
%T IVS1 £¿397T>C Estrogen Receptor ¦Á Polymorphism Is Associated with Low-Grade Systemic Inflammatory Response in Type 1 Diabetic Girls
%A Monika Ryba-Stanis£¿awowska
%A Karolina Rybarczyk-Kapturska
%A Agnieszka Brandt
%A Ma£¿gorzata My£¿liwiec
%A Jolanta My£¿liwska
%J Mediators of Inflammation
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/839585
%X Purpose. The study aimed to investigate the influence of estrogen receptor ¦Á (ER-¦Á) 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-¦Á genotyping was carried out by PCR. Serum concentrations of 17¦Â-estradiol, as well as IL-6, TNF-¦Á, 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-¦Á , and VEGF. The association between the level of certain cytokine and the genetic variant of estrogen receptor ¦Á 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 ¦Á 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. 1. Introduction One of the most analyzed genetic factors that control autoimmunity is polymorphism of certain genes, which in case of particular alleles contributes to the protection against some autoimmune diseases. Conversely, however, some genetic variants induce the development and the progression of such illnesses [1]. Another factor that affects autoimmunity is gender, and so females are thought to be more susceptible to develop autoimmune diseases [2¨C5]. The prevalence of autoimmune diseases in females may depend in part on the influence of sex hormones on the immune system [3, 6]. It is well known that the autoimmune response in some diseases is hampered during the pregnancy, when the levels of estrogens are high [3, 6]. Estrogens are able to induce the expansion of suppressor regulatory T cells (Tregs) [7¨C9], which makes them potentially protective factors in the development of autoimmune diseases. The function of Tregs was shown by us and others to be compromised in type 1 diabetic subjects [10¨C13]. Furthermore we have found that the level of Tregs, as well as their ability to express Foxp3, may depend in part on estrogen receptor ¦Á polymorphism,
%U http://www.hindawi.com/journals/mi/2014/839585/