title: Molecular scanning of interleukin-21 gene and genetic susceptibility to type 1 diabetes.
abstract: A recent study in the nonobese diabetic (NOD) mouse demonstrated the involvement of interleukin (IL)-21 in the pathogenesis of type 1 diabetes. A strong susceptibility locus, Idd3, has also been mapped to the interval containing the murine gene for IL-21 (Il21), making Il21 and the human orthologue IL21 a functional and positional candidate gene for type 1 diabetes. To investigate the contribution of the human genes for IL-21 and its receptor (IL-21R) to susceptibility to type 1 diabetes, we re-sequenced IL21 to identify novel sequence variants, searched for informative variants of IL21R, and studied the association of these variants with the disease. Two polymorphisms, a single nucleotide polymorphism (SNP) and a mononucleotide repeat polymorphism, were identified for IL21, and an allele of the mononucleotide repeat polymorphism was positively associated with the disease. Two novel microsatellite polymorphisms of IL21R were identified, one of which was associated with the disease. Scoring of individuals according to the status of these alleles showed a significant trend for high scores for susceptibility in diabetes patients, suggesting the contribution of IL21 and IL21R to disease susceptibility in an additive manner. These data suggest a contribution of IL21 and IL21R to genetic susceptibility to type 1 diabetes and possible involvement of IL-21 and its receptor system in the disease pathogenesis.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Asano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishino
authors.forename: Koji
authors.initials: K
authors.lastname: Nojima
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Noso
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hiromine
authors.forename: Aya
authors.initials: A
authors.lastname: Fukai
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D044466:Asian People / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D007438:Introns; D007564:Japan; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid; D000098546:Interleukin-21
chemical_list: C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D000098546:Interleukin-21