title: Impact of vitamin D receptor gene polymorphisms in pathogenesis of Type-1 diabetes mellitus.
abstract: BACKGROUND
  Type 1 diabetes mellitus (TIDM) results from an immune-mediated destruction of insulin-producing-cells in the pancreatic islets of Langerhans. There are clear differences in immunogenetic predisposition to type1 diabetes among countries. Studies have indicated that vitamin D supplementation in early childhood decreases the risk of TIDM. Vitamin D exerts its action via the nuclear vitamin D receptor (VDR), which shows an extensive polymorphism. VDR gene polymorphisms have been associated with altered gene expression or gene function. Four single nucleotide polymorphisms (SNPs) in the VDR gene produce variation in four recognition sites. These recognition sites variants include Fok I, Bsm I, Apa I and Taq I.
  
  
  OBJECTIVE
  TO investigate the relationship between VDR gene polymorphisms (at positions Taq I and Apa I) and the incidence of TIDM in Egyptian peoples.
  
  
  METHODS
  This study included 74 patients with type 1 DM in addition to 28 healthy age and sex matched control subjects. All of them were subjected to full history taking and clinical examination. Three ml of venous blood were withdrawn from each patient at fasting and postprandial times and used for genomic DNA extraction, estimation of Hb A1C, as well as, fasting and postprandial C-peptide and blood glucose levels.
  
  
  RESULTS
  Apa I recognition site was found in low frequency in diabetic patients (14/74) 18.9% while, its frequency was high (16/28) 57.1% among normal subjects. Taq I has two recognition sites. The first was found at nucleotide number 293 that was found in a frequency of (2/28) 7.1% in normal non-diabetic individuals while it was detected in (14/74) 18.9% in diabetic patients. The second Taq I recognition site was found at nucleotide number 494 without any differences between diabetic and normal individuals.
  
  
  CONCLUSIONS
  This study indicates that there is an association between VDR genetic polymorphism and incidence of TIDM in Egyptian patients.
authors: Department of Clinical Pathology, National Cancer Institute, Cairo University Egypt.
authors: Mahmoud M
authors: MM
authors: Kamel
authors: Department of Internal Medicine, Faculty of Medicine, Cairo University Egypt.
authors: Shawky A
authors: SA
authors: Fouad
authors: Department of Clinical Pathology, Ahmed Maher Education Hospital Egypt.
authors: Omina
authors: O
authors: Salaheldin
authors: Department of Pediatrics Egypt.
authors: Abd El-Rahman A Abd
authors: Ael-R
authors: El-Razek
authors: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University Egypt.
authors: Abeer I Abd
authors: AI
authors: El-Fatah
keywords: Vitamin D receptor (VDR); polymorphism; type 1 diabetes mellitus (TIDM)