Affiliations: [a] Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [b] Urogenital Stem Cell Research Center, Shahid Labbafi Nejad Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence:
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Corresponding author: Arezou Sayad, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, PO Box 1985717443, Tehran, Iran. Tel.: +98 21 23872572; Fax: +98 2122925814; E-mail: [email protected].
Abstract: BACKGROUND: Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reported to be associated with different immunologic disease. OBJECTIVE: Multiple Sclerosis (MS) patients have shown an aberrant blood level of soluble form of IL7R protein. The genomic changes in the sequence of this gene have been suggested to be correlated with its altered splicing specially, variants in the exon 6 of the gene have been reported to influence the maintenance or skipping of this exon and control the soluble or insoluble form of the final product. In order to evaluate this changes in the IL7RA gene and to determine a possible correlation between these changes and the MS susceptibility the whole sequence of the exon 6 and 7 and their flanking sequences were analyzed. METHODS: In this regard, we investigate the sequence changes of the exon 6 and 7 of the IL7RA gene in 75 relapsing-remitting MS patients and compare the results with 75 healthy control using sequence analyzing. RESULTS: The results of the sequence analysis were used in two aspects. The allelic and genotypic estimated frequencies of a reported risk variant rs6897932 in patients and controls in our population confirmed its association with the disease (P= 0.009, OR = 6.273, for TT genotype). Also, we report a possible hazardous cutoff for changes in a potential exon splicing silencer element (ESS (nt. 20–24)) and its correlation with rs6897932 to confer the risk of developing MS. CONCLUSION: In conclusion our results confirm the association between IL7RA exon 6 sequence changes and increased susceptibility for multiple sclerosis.
