Iranian Journal of Allergy, Asthma and Immunology 2017. 16(4):338-346.

Interleukin 7 Receptor Alpha Gene Variants Are Correlated with Gene Expression in Patients with Relapsing-remitting Multiple Sclerosis
Arezou Sayad, Mir Davood Omrani, Ghasem Solgi, Rezvan Noroozi, Shahram Arsang-Jang, Hidetoshi Inoko, Mohammad Taheri

Abstract


The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients.  Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p<0.0001).  A decreased level of mRNA expression for the membrane-bound IL-7Rα (mbIL-7Rα) and an increased level of mRNA for the soluble IL-7Rα (sIL-7Rα) were observed in patients versus controls (p=0.005 and p=0.002 respectively). A significant decreased level of mRNA expression for mbIL-7Rα (p=0.01) and an increased level of mRNA for sIL-7Rα (p=0.008) were observed in RRMS patients compared to healthy controls carrying the TT+CT genotypes. The higher levels of mRNA expression for the sIL-7Rα isoform in MS patients carrying the IL7R*TT genotype is a new finding not previously reported in studies on the genotype-induced effects of IL-7Rα expression in multiple sclerosis.

 


Keywords


Gene expression; IL7Rα gene; Multiple sclerosis; Polymorphism

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