A MOLECULAR STUDY OF HNF-1ALPHA GENE MUTATIONS IN MODY3 EGYPTIAN PATIENTS

Abstract

Maturity onset diabetes of the young type 3 (MODY3) is a heterogeneous monogenic form of diabetes mellitus caused by mutations in the gene of ''hepatocyte nuclear factor-1alpha'' (HNF-1alpha) which result in poor insulin secretion in response to glucose. The aim of the present study is to detect, for the first time in Egypt, the mutations in the HNF-1alpha gene in the Egyptian patients, and to compare the results for the Egyptian patients with those in other regions. This study included eight Egyptian patients diagnosed with MODY3; their ages were between 12 and 17 years old. DNA extraction was carried out from the blood samples, which were collected from the patients. Then, the polymerase chain reaction (PCR) was applied, in each sample, on exons 6, 7, 8, 9 and 10 and on promoter 1 of MODY3 gene (HNF-1alpha). Exon 9 was not amplified in all the attempts. The direct sequence analyses of the promoter 1 and the preceding exons of HNF-1alpha gene were detected. The obtained results of the sequences were aligned with the normal ones which were obtained from NCBI reference sequence database with the accession number NM_000545.5. The results yielded single nucleotide polymorphism (SNP), of which are the missense and silent mutations. The maximum number of variants was that of SNPs. The results of the present study showed that about 20 different SNPs were detected in the promoter 1. The obtained results of the exons were: (i) one novel missense mutation c.1304T>A obtained in the exon 6, (ii) two SNPs c.1501+7G>A (IVS7+7G>A) and c.1769-24T>C (IVS9-24T>C) detected in intron 7 and intron 9, respectively, (iii) two silent mutations, c.1375C>T and c.1545G>A found in the exon 7 and the exon 8, respectively; and (iv) one missense mutation c.1460G>A detected in the exon 7. The variants ii, iii and iv were previously recorded in other populations. Thus, from these results we can suggest that the mutations in the HNF-1alpha gene can contribute to MODY3 disease in the Egyptian population.