Allelic association of the interleukin 7 receptor gene (IL7R) with multiple sclerosis (MS). S.G. Gregory¹, S. Schmidt¹, J. Hart¹, A. Prokop¹, J. van der Walt¹, L.F. Barcellos², C. DeLoa³, J.R. Oksenberg³, S.L. Hauser³, J.L. McCauley⁴, M.A. Pericak-Vance¹, J.L. Haines⁴. 1) Dept Medicine, Ctr Human Genetics, Durham, NC; 2) School of Public Health, University of California, Berkeley; 3) Department of Neurology, University of California, San Francisco; 4) Center for Human Genetics Research, Vanderbilt University Medical Center.
   Multiple sclerosis (MS) is the prototypic human demyelinating disease, with evidence for genetic influences arising from numerous sibling risk, adoption and twin studies. The disease is most common in young adults, with less than 10% of identified cases beginning after the age of 55 and less than 5% before the age of 14. Females are 2-3 times more frequently affected than males and disease course can vary from some patients suffering major disability several decades post-diagnosis, while others reach wheelchair dependency within a few months or years upon onset. We identified 8 genes, from eight published MS RNA expression analyses, that were differentially expressed within at least two of the studies. SNPs within one of these candidate genes, the interleukin 7 receptor gene (IL7R), are significantly associated with MS by PDT analysis within our combined dataset of almost 950 patients and their relatives. One SNP, localizing to alternatively spliced transmembrane domain of the protein, shows strongest association with risk (p=0.00006). Two independent studies have previously implicated IL7R with primary progressive MS, however, our analysis finds that this gene is also associated with the risk of developing the more common relapsing-remitting MS. Our result implicating the involvement of IL7R, therefore, not only represents a functionally relevant gene involved with the risk of MS development but also the replication of two previous studies. Molecular work to investigate the effect that the coding SNP has upon the functioning of the protein is currently underway.