Molecular analysis of the eukaryotic translation initiation factor 2B5 EIF2B5 gene in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an encumbering inflammatory condition of the nervous newlinesystem in which there occurs axonal demyelination. There is sufficient evidence newlinesuggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family in newlinecausing vanishing white matter (VWM) disease of the brain. Incidentally researchers newlinehave proposed overlapping between MS and VWM in terms of clinical, biochemical newlineand genetic aspects, which incited us to explore the association between EIF2B and newlineMS. eIF2B plays an essential role in translation initiation and its regulation in newlineeukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a newlinecrucial epsilon (and#949;) subunit of the eIF2B protein as most of the alterations have been newlinefound in this gene, which impelled us to screen it in a subset of Indian population. To newlinedetermine whether sequence alterations in EIF2B gene family are involved in newlinepredisposing Kashmiri population to MS, we screened different exons of its EIF2B5 newlinegene. To the best of our knowledge, the correlation of EIF2B5 with MS susceptibility newlinehas not been studied so far in Asian continent and our study is the first in this newlinedirection. newlineIn the present study we analyzed 16 exons as well as introns of EIF2B5 for sequence newlinevariations in 41 MS patients and 123 age and gender matched healthy controls (a total newlineof 164 participants) from Kashmir Valley of India. Most of the patients examined in newlinethis study had relapsing remitting (RR) course of MS and only few had secondary newlineprogressive (SP) and primary progressive (PP). In case of MS patients, male to female newlineratio was 1:3.1, suggesting female predominance, which is in consensus with already newlinepublished reports across the globe. Sequence analysis revealed four heterozygous newlinesingle nucleotide polymorphisms (SNPs) in EIF2B5: cDNA702AgtG (c.580AgtG), newlinecDNA733CgtT (c.611CgtT), c.1745+134AgtG and cDNA1881AgtG (c.1759AgtG). newlineAmong them, 702AgtG and 733CgtT were found in Exon 4 in Codon 194 and Codon newline204 respectively, c.1745+134AgtG in Intron 12 and 1881AgtG in Exon 13 in Codon newline587......