title: A population-based study of IL4 polymorphisms in multiple sclerosis.
abstract: Previous studies have suggested a role for interleukin-4 gene (IL4) in susceptibility to multiple sclerosis (MS) as well as other autoimmune diseases. We screened the promoter region, exons 1-4 and their splice sites for polymorphisms and tested the association between novel polymorphisms E1(33)*C-->T and I3(2580)*C-->A, and the established 5'(-523)*C-->T and I3(709)*VNTR polymorphisms with susceptibility to, age of onset in, and course and severity of MS in sporadic cases. I3(709)*VNTR was associated with susceptibility to MS (p=0.004) due to a dearth of heterozygotes in patients (29/122; 23.8%) compared to controls (91/244; 37.3%). Homozygotes for the uncommon I3(709)*allele-2 may have increased susceptibility (p=0.044; OR=5.17, 95% CI: 0.83-54.95) as might carriers for the extended haplotypes 5'(-523)*T/E1(33)*T/I3(709)*allele-2/I3(2580)*C (p=0.003; OR: 3.75, 95% CI: 1.18-11.93) or 5'(-523)*C/E1(33)*C/I3(709)*allele-1/I3(2580)*A (p=0.004; OR: 4.22, 95% CI: 1.22-14.54). We could not confirm the previously reported association between carriage of I3(709)*allele-2 and older age of onset. However, we found a trend for association between the homozygous state for this allele and older age of onset.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, 200 First Street, SW, Rochester, MN 55905, USA.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
authors.forename: Janet L
authors.initials: JL
authors.lastname: Schaefer-Klein
authors.forename: David D
authors.initials: DD
authors.lastname: Hebrink
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Achenbach
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.forename: Cynthia T
authors.initials: CT
authors.lastname: McMurray
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000276:immunology; D016001:Confidence Intervals; D006239:Haplotypes / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008910:Minnesota / Q000453:epidemiology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D015847:Interleukin-4