Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression

Abstract

Multiple sclerosis (MS) is a common demyelinating neurodegenerative disease with a strong genetic component. Previous studies have associated genetic variants in IL2RA and IL7R in the pathophysiology of the disease. In this study we describe the association between IL2RA (rs2104286) and IL7R (rs6897932) in the Canadian population. Genotyping 1,978 MS patients and 830 controls failed to identify any significant association between these variants and disease risk. However, stratified analysis for family history of disease, and disease course identified a trend towards association for IL2RA in patients without a family history (p = 0.05; odds ratio = 0.77), and a significant association between IL7R and patients who developed progressive MS (PrMS) (p = 0.002; odds ratio = 0.73).Although not statistically significant, the effect of IL2RA (rs2104286) in patients without a family history of MS indicates that the genetic components for familial and sporadic disease are perhaps distinct. This data suggests the onset of sporadic disease is likely determined by a large number of variants of small effect, whereas MS in patients with a family history of disease is caused by a few deleterious variants. In addition, the significant association between PrMS and rs6897932 indicates that IL7R may not be disease-causing but a determinant of disease course. Further characterization of the effect of IL2RA and IL7R genetic variants in defined MS subtypes is warranted to evaluate the effect of these genes on specific clinical outcomes and to further elucidate the mechanisms of disease onset and progression.

Nuclear Receptor NR1H3 in Familial Multiple Sclerosis

“…All samples were collected through the longitudinal Canadian Collaborative Project on the Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) (Sadovnick et al, 1998;Traboulsee et al, 2014). The ethical review board at the University of British Columbia approved the study, and all participants provided informed consent.…”

Purinergic receptorsP2RX4andP2RX7in familial multiple sclerosis

“…Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by myelin loss, axonal pathology, and progressive neurological dysfunction. The etiology of MS is complex with both genetic and environmental factors implicated in disease susceptibility, with the human leucocyte antigen‐DRB1 region providing the highest known attributable risk (Traboulsee et al., ). Recently, functional variants in genes for the purinergic receptors P2RX7 (MIM# 602566) and P2RX4 (MIM# 600846) have been shown to modulate MS susceptibility (Gu et al., ).…”

Association between CD127 Gene Polymorphism and Susceptibility to Multiple Sclerosis

“…These failures to demonstrate association between risk of MS and CD127 gene polymorphisms might be due to low sample size of these studies, similar to our study in which we studied 200 RRMS patients. But it should be considered although low sample size can affect results of these studies, large sample sizes might be yielded similar results, as Traboulsee, et al [13] studied IL7Ra gene polymorphism among 1,978 Canadian MS patients and they also failed to find association between this SNP and susceptibility to MS (p value = 0.07), however, they found significant association between IL7R and patients who developed Progressive MS (PRMS) (p = 0.002; odds ratio = 0.73).…”