Analysis of IL4R haplotypes in predisposition to multiple sclerosis

Abstract

We have investigated the association of multiple sclerosis (MS) with polymorphisms in the IL4R gene in 332 single-case MS families. IL4R encodes a subunit of the interleukin-4 receptor, a molecule important for T-cell development and differentiation, and is a gene shown to be associated with immune-related diseases such as asthma and type I diabetes. By genotyping two promoter and eight coding IL4R SNPs and identifying haplotypes (complex alleles) in the MS families, stratified for HLA genotype, we have observed evidence of the association of the IL4R gene to MS. In particular, we have identified a specific susceptibility haplotype, and observe that the risk is conferred primarily to individuals not carrying the high MS-risk HLA DR2 (DRB1*1501-DQB1*0602) haplotype (nominal P ¼ 0.009). These findings suggest a potentially important role for the IL4R gene in predisposition to MS, and provide further evidence of its relevance as a candidate gene for immune-related diseases.

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

“…These tested IL4R markers did not show any significant association in the SWE II material (data not shown). The rs1801275 marker that was part of the associated haplotype in the SWE I cohort, and has been analyzed in several published investigations, [32][33][34] was genotyped in the NOR and SWE II materials and an overall association analysis was performed including reports in the literature. There was no association for this IL4R marker, nor was there significant heterogeneity between the materials ( Figure 6).…”

“…There was no association for this IL4R marker, nor was there significant heterogeneity between the materials ( Figure 6). Further, given a previous report that suggested that the IL4R association is mainly observed among DR2-positive MS patients, 32 we repeated the meta-analysis stratified for DR2 for the SWE I, SWEII and NOR materials, but no significant association for rs1801275 was observed (data not shown).…”

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

“…The IL-4R gene is located at 16p11-12. Substitution of amino acid residues, particularly by the non-synonymous SNP Gln551Arg (rs1801275), has been reported to be functionally important and to impact upon IL-4R signalling (Mirel et al, 2004). This SNP has been found to be significantly associated with various immune-related diseases such as asthma and atopy (Hytönen et al, 2004;Sandford et al, 2000) and connective tissue disease (Youn et al, 2000).…”

Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

“…Interestingly, we have recently reported the transmission distortion and significant association of a 10-SNP IL4R haplotype with MS in HLA-DR15-negative white nuclear families. 19 Transmis- Association study of multiple sclerosis in African Americans D Brassat et al sion distortion of IL4R alleles were also reported in a Belgian trio families MS data set. 20 Taken together, the latter and current reports provide accumulating evidence for a potential role for the IL4 receptor and its ligand, IL-4, in MS susceptibility and pathogenesis.…”