title: Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-alpha gene and their associations with multiple sclerosis.
abstract: 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.
authors.affiliation: Institute for Immunology and Allergy Research (Westmead Millennium Institute), Westmead Hospital, Westmead, NSW 2145, Australia. suzyt@westgate.wh.usyd.edu.au
authors.forename: Suzy M
authors.initials: SM
authors.lastname: Teutsch
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Bennetts
authors.forename: Robert N S
authors.initials: RN
authors.lastname: Heard
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Stewart
mesh_terms: D001315:Australia / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain