Vitamin D binding protein gene polymorphisms and risk of type 1 diabetes mellitus among Egyptians

Type 1 diabetes (T1DM) is a multifactorial autoimmune disease in which both genetic predisposition and environmental factors participate in its development. Many cellular and epidemiological studies suggest a role for vitamin D in pathogenesis and prevention of T1DM. Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to T1DM. Vitamin D-binding protein (DBP) is the main systemic transporter of vitamin D and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GAT→GAG substitution replaces aspartic acid by glutamic acid in codon 416; and ACG→AAG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for vitamin D. Few published studies, about the correlation between these alleles and T1DM, yielded conflicting results. Therefore, we investigated the association of these polymorphisms with T1DM in Egyptian subjects. Unrelated 59 children with T1DM and 65 healthy controls were included in this study. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined using Restriction Fragment Length Polymorphism analysis (RFLP). At codon 416 the frequency of Glu/Asp alleles was 64.4/35.6% in T1DM patients and 55.4/44.6% in controls (P >0.05). At codon 420 the frequency of Thr/Lys alleles were 88.1/11.9% and 87.7/12.3% (P >0.05), respectively. Distributions of genotypes at both loci, and the common haplotypes constructed by them, were also very similar in both groups (P >0.05). It could be concluded that the studied DNA polymorphisms in the DBP gene are not associated with T1DM in Egyptian patients.Key words: Type 1 diabetes Mellitus (T1DM), Vitamin D binding protein (DBP), polymorphis

Relation of HCV induced insulin resitance and Hepatocellular carcinoma: Role of MDR1 gene C.335t>C and C.3073A>C SNPS

Hepatocellular carcinoma (HCC), is the most common primary liver tumor. HCV-associated insulin resistance (IR) may cause hepatic steatosis, hepatic fibrosis and hepatocarcinogenesis. The multidrug resistance 1 gene (MDR1) is a candidate gene for susceptibility to HCC.. The aim of the current study was to evaluate the association of the MDR 1 gene c.335T>C and the c.3073A>C SNPs with HCV induced HCC and to correlate this toinsulin resistance state. A total of 205 HCC patients (on top of HCV) were enrolled in this study. Genotyping of MDR1 gene SNPs was done by PCR-RFLP.Results revealed that the association of genotypes/alleles from the c.335T.C and c.3073A.C SNPs with the risk of HCC. There was a significantly increased risk of HCC in chronic HCV that was associated with hepatic steatosis. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to theTT genotype.It could be concluded from this work that HCV-related metabolic complications as hepatic steatosis and IR may be associatedwith increased risk of HCC development. c.335T>C and c.3073A>C SNPs of MDR1 gene could be considered as a possible molecular candidates for the HCC development in chronic HCV patients.Key words: HCV-HCC-Insulin Resistance -steatosis-MDR1genepolymorphis