Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis

• Published in: Multiple sclerosis Vol. 17; no. 8; pp. 922 - 930
• Main Authors: Sombekke, MH, van der Voort, LF, Kragt, JJ, Nielsen, JM, Guzel, H, Visser, A, Oudejans, CBM, Crusius, JBA, Peña, A Salvador, Vrenken, H, Polman, CH, Killestein, J
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.08.2011; Sage Publications; Sage Publications Ltd
• Subjects: Alleles; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Genetic Predisposition to Disease; Genotype; Humans; Medical sciences; Multiple Sclerosis - genetics; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Netherlands; Neurology; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptors, Interleukin-7 - genetics; RNA, Messenger - analysis; Netherlands; phenotype; genetics; MRI; multiple sclerosis; mRNA; IL7R; genotype; Human; Nervous system diseases; Multiple sclerosis; Genotype; Nuclear magnetic resonance imaging; Inflammatory disease; Phenotype; Central nervous system disease; Degenerative disease; Dutch
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458511402411

Background: The interleukin 7 receptor (IL7R) has been recognized as a susceptibility gene for Multiple Sclerosis (MS). Analysis of rs6897932 (the most strongly MS-associated single nucleotide polymorphism (SNP)), showed effects of genotype on the relative expression of membrane-bound to total amount of IL7R mRNA. Objective: We assessed the relevance of IL7R on MS phenotype (including clinical and magnetic resonance imaging (MRI) parameters) at DNA and mRNA level in Dutch patients with MS. Methods: The genotype of rs6897932 was analyzed in 697 patients with MS and 174 healthy controls. The relevance of genotype and carriership of the C allele on MS phenotype (disease activity and severity, using clinical and MRI parameters) was assessed. In addition, relative gene expression of membrane-bound to total IL7R mRNA was analyzed with respect to disease phenotype in a subgroup of 95 patients with early relapsing MS. Results: In particular, homozygosity for the risk allele is a risk factor for MS in our population (ORCC vs CT and TT = 1.65 (95% CI: 1.18–2.30), two-sided p = 0.004). However, no effect of genotype or the relative expression of membrane-bound IL7R (presence of exon 6–7) to total amount of IL7R mRNA (presence of exon 4–5) was found on MS phenotype. Discussion: Homozygosity for the IL7R exon 6 rs6897932 C allele is associated with a higher risk for MS in our Dutch population. No effect was found of genotype or mRNA expression on disease phenotype.