Eur J Hum Genet. 2003 Jul;11(7):509-15
Teutsch SM, Booth DR, Bennetts BH, Heard RN, Stewart GJ.
Institute for Immunology and Allergy Research (Westmead Millennium Institute), Westmead Hospital, Westmead, NSW 2145, Australia
The University of Sydney, NSW 2006, Australia.
We have investigated the interleukin-7 receptor (IL-7R) alpha-chain gene as a positional and functional candidate gene for susceptibility to multiple sclerosis (MS), in view of its chromosomal location on 5p14-p12, a region that has shown suggestive linkage in MS genome screens, and its role in T- and B-cell proliferation and reactivity.
Amplification and DNA sequencing of the IL-7Ralpha gene in pooled and individual samples identified 13 single nucleotide polymorphisms (SNPs), 11 of which are novel, including three in the promoter region, three in exons encoding amino-acid changes (ACC(Thr)66ATC(Ile), ATC(Ile)244ACC(Thr), ATC(Ile)336GTC(Val)), four in introns and one in the 3' untranslated region.
Four IL-7R haplotypes were identified for nine SNPs, showing linkage disequilibrium across the gene, and allowing haplotype frequency determination from just three of the nine SNPs.
Genotyping of the -504 polymorphism in 101 MS and 90 controls showed a suggestive (P=0.1) association of the T allele with MS; however, this was not supported by transmission disequilibrium testing in 186 MS trio families (P=0.8).
There were trends towards an increase of the GTG+ haplotype (odds ratio=1.45), and under-representation of the TTA+ haplotype (OR=0.65) in DRB1(*)1501-positive MS cases, suggesting that larger sample sizes and comparison in more defined MS patient groups may support an association with the IL-7R gene.
These polymorphisms would also be useful for studying genetic associations with other immunologic diseases.