title: Trinucleotide repeats of programmed cell death-1 gene are associated with susceptibility to type 1 diabetes mellitus.
abstract: Multiple genes are involved in conferring susceptibility to autoimmune type 1 diabetes mellitus. The immunoreceptor programmed cell death-1 (PDCD-1), an inhibitory costimulatory molecule regulating peripheral tolerance, is reported to play an important role in the development of type 1 diabetes mellitus, making the human PDCD-1 gene, PDCD1, a candidate for disease susceptibility. The aim of this study was to clarify the contribution of PDCD1 to genetic susceptibility to type 1 diabetes mellitus in humans. To screen for sequence variants, we sequenced all 5 exons and exon-intron junctions of PDCD1 in Japanese subjects, 16 with type 1 diabetes mellitus and 16 without the disease. Some of the sequence variations identified were genotyped in larger samples (n = 275) with and without type 1 diabetes mellitus by polymerase chain reaction restriction fragment length polymorphism method or a fluorescence-based method. The distributions of polymorphisms were compared between patients with type 1 diabetes mellitus and healthy controls by contingency table analysis and Pearson chi(2) test. In this study, we found 16 sequence variants, including a TGC repeating variant in the 3' untranslated region. We found this variant to be associated with the development of type 1 diabetes mellitus. These data suggest the contribution of PDCD1 and its gene product to the development of type 1 diabetes mellitus.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hiromine
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
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: Katsuaki
authors.initials: K
authors.lastname: Asano
authors.forename: Aya
authors.initials: A
authors.lastname: Fukai
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D018911:Trinucleotide Repeats
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor