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, Childrenʼs
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
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.