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Effect of Estrogen Receptor- Alpha Gene Polymorphism (IVS1-397 T>C) on Microvascular Complications of Type 1 Diabetes Mellitus

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Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease whose etiology involves genetic predisposition as well as environmental factors. Polymorphisms of some genes are among the most important genetic factors that influence autoimmunity. Gender is another important factor affecting autoimmunity. Females are more susceptible to autoimmune diseases which may be due to the effect of sex hormones on the immune system activity. The metabolic effects of estrogen are mediated through its receptor – alpha. The exact mechanism is not well understood. A number of polymorphisms have been reported in the Estrogen Receptor- alpha (ER-alpha) IVS1 397 T>C gene which may be involved in the pathogenesis of diabetes.

Objectives: To assess the influence of Estrogen Receptor- alpha gene [IVS1-397 T>C] polymorphism on vascular complications of type1 diabetes mellitus in pubertal females and on the glycemic control.

Methods: This cross-sectional case-control study included 40 pubertal regularly menstruating girls less than 18 years with type 1 diabetes mellitus recruited from the Pediatric Diabetes Clinic, Children's Hospital, Ain-Shams University and 20 healthy age-and sex-matched controls. Estrogen receptor alpha genotypes were analyzed by Restriction Fragment Length PCR and correlated with both clinical and laboratory parameters in the studied cases. ER-alpha was chosen as it might play a role in diabetes pathogenesis.

Results: The study revealed the TC genotype was the most prevalent genotype of the estrogen receptor. The TT genotype patients had a younger age of onset of T1DM. The prevalence of obesity was higher among TC and TT than in CC bearing patients. In addition, CC genotype patients had the least prevalence of microalbuminuria and had better glycemic control than other genotypes.

Conclusion: Our findings suggest that Estrogen receptor- alpha gene may be affecting the age of onset of Type1 diabetes mellitus in pubertal girls as well as the glycemic control of these patients, where CC bearing girls had better glycemic control than other genotypes and less incidence of microalbuminuria.
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Keywords: Diabetes mellitus; IVS1- 397 T>C; estrogen receptor- alpha; girls; puberty; type 1

Document Type: Research Article

Publication date: September 1, 2020

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  • Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy.

    The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.
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