Interleukin 2 Receptor α Gene Polymorphism and Risk of Multiple Sclerosis: A Meta-Analysis

Abstract

This meta-analysis studied the association between interleukin 2 receptor a (IL2RA) gene polymorphisms rs2104286 and rs12722489 and susceptibility to multiple sclerosis (MS). Case-control genetic association studies published before January 2011 were retrieved from the PubMed and EMBASE databases and the Cochrane Library. Eight studies comprising 13 569 patients and 23 435 controls met the selection criteria for metaanalysis of the IL2RA rs2104286 polymorphism. Using a fixed-effects model, the T allele and the TT and TT + TC genotypes of the IL2RA rs2104286 polymorphism were found to be associated with MS. Five studies comprising 5643 patients and 6415 controls met the selection criteria for meta-analysis of the IL2RA rs12722489 polymorphism. Using a fixed-effects model, the C allele and the CC genotype of the IL2RA rs12722489 polymorphism were found to be associated with MS but the CC + CT genotype was not. It was concluded that both of the IL2RA gene polymorphisms, rs2104286 and rs12722489, were associated with increased susceptibility to MS.

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

“…A priori power analysis assuming a disease prevalence of 0.001, [1] with a minor allele frequency of 0.25, as observed in Caucasian populations, and the previously described relative risk of 1.25, [8,9] indicated that our series (n=2,808) has a 93% probability of identifying nominally significant differences in genotype frequencies between MS patients and controls. Analysis of MS subgroups, assuming the same parameters, indicated a statistical power of 91% for familial MS, 59% for sporadic MS, 83% for RRMS and 79% for progressive MS (PrMS; PPMS and SPMS).…”

“…[18,19] The goal of this study is to further define the role of IL2RA rs2104286 and IL7R rs6897932 in the susceptibility to MS. To this end, we characterized these two variants in a case-control series of MS patients from Canada. This cohort is noticeably distinct from those described in most association studies of IL2RA and IL7R with MS, [8,9] as it contains a higher proportion of patients with a family history of disease (82.5%), as well as a higher number of patients presenting PPMS (25%). Interestingly neither variant resulted in a significant association with disease in the entire cohort (Table 1) despite having a 93% power of detection.…”

“…[4,5] Outside of the HLA region, interleukin 2 receptor alpha (IL2RA) and interleukin 7 receptor (IL7R) are two of the genes more consistently found associated with risk of MS. [6,7] A meta-analysis of IL2RA rs2104286 and IL7R rs6897932 have confirmed these associations in the Caucasian population, [8,9] including Canadian patients. [10] Interestingly, one study found IL7R rs6897932 to be exclusively associated with patients presenting primary progressive MS (PPMS) and secondary progressive MS (SPMS), suggesting IL7R may have an effect on the development of a progressive disease course.…”

“…[4] Two of the non-HLA variants which have been substantially replicated in independent studies, albeit not consistently, are the rs2104286 in IL2RA and rs6897932 in IL7R. [8,9] These two genes are plausible biological candidates for MS since the proteins they encode, interleukin 2 receptor alpha (IL2Rα, also known as CD25) and interleukin 7 receptor alpha (IL7Rα, also known as CD127), play a fundamental role in lymphocyte development and the modulation of T cell effector function. [18,19] The goal of this study is to further define the role of IL2RA rs2104286 and IL7R rs6897932 in the susceptibility to MS. To this end, we characterized these two variants in a case-control series of MS patients from Canada.…”

“…Although significant associations were not identified, carriers of the rs2104286 G allele presented a protective odds ratio (OR) of 0.87 (95% CI = 0.74-1.03) (Figure 1), similar to those previously reported. [8,7] To further characterize the role of IL2RA in MS, we performed stratified association analyses according to family history of disease, as well as disease progression. Differences in rs2104286 genotypic or allelic frequencies were not observed between healthy controls and patients with positive family history of disease or progressive disease (Table 1).…”