title: Association of the interleukin-1 receptor antagonist gene with asthma.
abstract: The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-locus haplotype analysis of SNPs yielded several significant results (p < 0.05-0.0021) for the human IL1RN gene encoding the IL-1 receptor antagonist protein, an antiinflammatory cytokine that plays an important role in maintaining the balance between inflammatory and antiinflammatory cytokines. These findings were replicated and confirmed in an independent Italian family sample in which significant, although weaker, association with asthma was detected. A sequencing approach to the coding region of the human IL1RN gene revealed additional DNA variants, from which a selection was also associated with the disease in German and Italian samples. Calculation of the linkage disequilibrium for the human IL1RN gene showed strong linkage disequilibrium for nearly all analyzed SNPs. Further haplotype analysis indicated that six SNPs are sufficient for tagging all haplotypes with a prevalence of more than 1%. The most frequent haplotype constructed from these SNPs was 1.4-fold overtransmitted in the German family sample.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Margret
authors.initials: M
authors.lastname: Bahnweg
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Elisabeth
authors.initials: E
authors.lastname: André
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Nicole
authors.initials: N
authors.lastname: Herbon
authors.forename: Monika
authors.initials: M
authors.lastname: Werner
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Lydia
authors.initials: L
authors.lastname: Pescollderungg
authors.forename: Attilio
authors.initials: A
authors.lastname: Boner
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
mesh_terms: D001249:Asthma / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005815:Genetic Code / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D013548:Sweden / Q000453:epidemiology
chemical_list: D017472:Receptors, Interleukin-1