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01-09-2016 | Original Article

Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis

Authors: Song Wu, Qian Liu, Ji-Min Zhu, Ming-Rui Wang, Jing Li, Mei-Guo Sun

Published in: Neurological Sciences | Issue 9/2016

Abstract

The aim of this study was to explore the association between the IL7R T244I polymorphism (rs6897932) and susceptibility of multiple sclerosis (MS). A comprehensive literature search for relevant studies was conducted on Google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated. Seventeen case–control studies were included in this meta-analysis. In total, 17 articles provided data for 15,270 cases and 17,971 controls. The results showed significant association between the IL7R T244I polymorphism and susceptibility to MS (OR = 1.125, 95 % CI: 1.016–1.245, p = 0.024 for C vs. T; OR = 1.176, 95 % CI: 1.078–1.282, p < 0.001 for CC + CT vs. TT; OR = 1.243, 95 % CI: 1.088–1.421, p = 0.001 for CC vs. TT). Stratified analysis of ethnicities also showed significant association in Europeans. However, no association was found in Asians. This study suggested that the IL7R C allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the roles played by the IL7R T244I polymorphism during the pathogenesis of MS.

Compston A, Coles A (2008) Multiple sclerosis. Lancet 372(9648):1502–1517CrossRefPubMed

Noseworthy JH (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399(6738 Suppl):A40–A47CrossRefPubMed

Jonasdottir A, Thorlacius T, Fossdal R et al (2003) A whole genome association study in Icelandic multiple sclerosis patients with 4804 markers. J Neuroimmunol 143(1–2):88–92CrossRefPubMed

Husain S, Yildirim-Toruner C, Rubio JP et al (2008) Variants of ST8SIA1 are associated with risk of developing multiple sclerosis. PLoS One 3(7):e2653CrossRefPubMedPubMedCentral

Pathak K (2014) The expanding role of IL-7 and thymic stromal lymphopoietin as therapeutic target for rheumatoid arthritis. Expert Opin Ther Targets 18(5):581–594CrossRefPubMed

Kelly EA, Koziol-White CJ, Clay KJ et al (2009) Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. J Immunol 182(3):1404–1410CrossRefPubMedPubMedCentral

McKay FC, Swain LI, Schibeci SD et al (2008) CD127 immunophenotyping suggests altered CD4⁺ T cell regulation in primary progressive multiple sclerosis. J Autoimmun 31(1):52–58CrossRefPubMed

Li L, Masucci MG, Levitsky V (2000) Effect of interleukin-7 on the in vitro development and maturation of monocyte derived human dendritic cells. Scand J Immunol 51(4):361–371CrossRefPubMed

Kreft KL, Verbraak E, Wierenga-Wolf AF et al (2012) Decreased systemic IL-7 and soluble IL-7Ralpha in multiple sclerosis patients. Genes Immun 13(7):587–592CrossRefPubMed

10.

Fang L, Isobe N, Yoshimura S et al (2011) Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians. Neurology 76(24):2125–2127CrossRefPubMed

11.

Alcina A, Fedetz M, Ndagire D et al (2008) The T244I variant of the interleukin-7 receptor-alpha gene and multiple sclerosis. Tissue Antigens 72(2):158–161CrossRefPubMed

12.

Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748PubMed

13.

DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28(2):105–114CrossRefPubMed

14.

Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558CrossRefPubMed

15.

Gregory SG, Schmidt S, Seth P et al (2007) Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 39(9):1083–1091CrossRefPubMed

16.

O’Doherty C, Alloza I, Rooney M, Vandenbroeck K (2009) IL7RA polymorphisms and chronic inflammatory arthropathies. Tissue Antigens 74(5):429–431CrossRefPubMed

17.

Ramagopalan SV, Anderson C, Sadovnick AD, Ebers GC (2007) Genomewide study of multiple sclerosis. N Engl J Med 357(21):2199–200. (author reply 2200–1)

18.

Weber F, Fontaine B, Cournu-Rebeix I et al (2008) IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes Immun 9(3):259–263CrossRefPubMed

19.

Svejgaard A (2008) The immunogenetics of multiple sclerosis. Immunogenetics 60(6):275–286CrossRefPubMed

20.

Akkad DA, Hoffjan S, Petrasch-Parwez E, Beygo J, Gold R, Epplen JT (2009) Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients. J Autoimmun 32(2):110–115CrossRefPubMed

21.

Kallio SP, Jakkula E, Purcell S et al (2009) Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS. Hum Mol Genet 18(9):1670–1683CrossRefPubMedPubMedCentral

22.

Stankovic A, Dincic E, Ristic S et al (2010) Interleukin 7 receptor alpha polymorphism rs6897932 and susceptibility to multiple sclerosis in the Western Balkans. Mult Scler 16(5):533–536CrossRefPubMed

23.

Sombekke MH, van der Voort LF, Kragt JJ et al (2011) Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis. Mult Scler 17(8):922–930CrossRefPubMed

24.

Jager J, Schulze C, Rosner S, Martin R (2013) IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis. Genes Immun 14(7):453–461CrossRefPubMed

25.

Rubio JP, Stankovich J, Field J et al (2008) Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun 9(7):624–630CrossRefPubMed

26.

Heidari M, Behmanesh M, Sahraian MA (2011) Variation in SNPs of the IL7Ra gene is associated with multiple sclerosis in the Iranian population. Immunol Invest 40(3):279–289CrossRefPubMed

27.

Majdinasab N, Hosseini BM, Galehdari H, Mohaghegh M (2014) Association of interleukin 7 receptor gene polymorphism rs6897932 with multiple sclerosis patients in Khuzestan. Iran J Neurol 13(3):168–171PubMedPubMedCentral

28.

Hafler DA, Compston A, Sawcer S et al (2007) Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357(9):851–862CrossRefPubMed

29.

Ribeiro AR, Rodrigues PM, Meireles C, Di SJP, Alves NL (2013) Thymocyte selection regulates the homeostasis of IL-7-expressing thymic cortical epithelial cells in vivo. J Immunol 191(3):1200–1209CrossRefPubMed

30.

Haralambieva IH, Ovsyannikova IG, Kennedy RB et al (2011) Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination. Vaccine 29(45):7883–7895CrossRefPubMedPubMedCentral

31.

Heron M, Grutters JC, van Moorsel CH et al (2009) Variation in IL7R predisposes to sarcoid inflammation. Genes Immun 10(7):647–653CrossRefPubMed

32.

Lundstrom W, Highfill S, Walsh ST et al (2013) Soluble IL7Ralpha potentiates IL-7 bioactivity and promotes autoimmunity. Proc Natl Acad Sci USA 110(19):E1761–E1770CrossRefPubMedPubMedCentral

33.

O’Connor AM, Crawley AM, Angel JB (2010) Interleukin-7 enhances memory CD8(+) T-cell recall responses in health but its activity is impaired in human immunodeficiency virus infection. Immunology 131(4):525–536CrossRefPubMedPubMedCentral

34.

Zhou J, Jin JO, Du J, Yu Q (2015) Innate immune signaling induces IL-7 production, early inflammatory responses, and Sjogren’s-like dacryoadenitis in C57BL/6 mice. Invest Ophthalmol Vis Sci 56(13):7831–7838CrossRefPubMedPubMedCentral

35.

Arbelaez CA, Glatigny S, Duhen R, Eberl G, Oukka M, Bettelli E (2015) IL-7/IL-7 receptor signaling differentially affects effector CD4⁺ T Cell subsets involved in experimental autoimmune encephalomyelitis. J Immunol 195(5):1974–1983CrossRefPubMed

36.

Mazzucchelli RI, Riva A, Durum SK (2012) The human IL-7 receptor gene: deletions, polymorphisms and mutations. Semin Immunol 24(3):225–230CrossRefPubMed

37.

Stahl EA, Raychaudhuri S, Remmers EF et al (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42(6):508–514CrossRefPubMedPubMedCentral

38.

Hartling HJ, Thorner LW, Erikstrup C et al (2013) Polymorphisms in the interleukin-7 receptor alpha gene and mortality in untreated HIV-infected individuals. AIDS 27(10):1615–1620CrossRefPubMed

39.

Hartling HJ, Thorner LW, Erikstrup C et al (2014) Polymorphism in interleukin-7 receptor alpha gene is associated with faster CD4(+) T-cell recovery after initiation of combination antiretroviral therapy. AIDS 28(12):1739–1748CrossRefPubMed

40.

Zenatti PP, Ribeiro D, Li W et al (2011) Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet 43(10):932–939CrossRefPubMed

Title: Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis
Authors: Song Wu
Qian Liu
Ji-Min Zhu
Ming-Rui Wang
Jing Li
Mei-Guo Sun
Publication date: 01-09-2016
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 9/2016
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-016-2608-8

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Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis

Abstract

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