title: Relationship of polymorphisms of the Interleukin-1 gene cluster to occurrence and severity of rheumatoid arthritis.
abstract: Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). We investigated whether IotaL-1 gene locus polymorphisms are associated with susceptibility to or severity of RA. Genotyping for IL-1alpha, IL-1beta and IL-1Ra single nucleotide polymorphisms (SNPs) performed in a cross-sectional group of 312 consecutive RA patients (RA-group 1) and a cohort of 94 incident female RA patients (RA-group 2) revealed that the rare IL-1RN + 2017 C allele was significantly increased in RA compared to controls (n = 245). A retrospective analysis in RA-group 1 showed no significant associations between IL-1 genotypes and disease severity. A prospective study in RA-group 2 demonstrated that the extent of joint destruction over 12 years was higher in patients genotyped heterozygous for the IL-1 A + 4845, IL-1B + 3953 and IL-1RN + 5111 SNPs compared to homozygous wildtype patients, although differences did not reach statistical significance. These data indicate that the IL-1RN + 2017 polymorphism is associated with susceptibility to RA.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: H
authors.initials: H
authors.lastname: van Dongen
authors.forename: A M
authors.initials: AM
authors.lastname: Bakker
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000494:pharmacology; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D007375:Interleukin-1