title: Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison's disease.
abstract: Although autoimmune Addison's disease (AAD) may occur as a component of the monogenic autoimmune polyendocrinopathy type 1 syndrome (APS1), it is most commonly found as an isolated disorder or associated with the autoimmune polyendocrinopathy type 2 syndrome (APS2). It is likely that sporadic (non-APS1) AAD is inherited as a complex trait; however, apart from the major histocompatibility complex, the susceptibility genes remain unknown. We have examined polymorphisms at two non-major histocompatibility complex candidate susceptibility loci in sporadic (non-APS1) AAD: the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and the autoimmune regulator (AIRE-1) gene. DNA samples from AAD subjects (n = 90) and local controls (n = 144 for CTLA-4; n = 576 for AIRE-1) were analyzed for the CTLA-4A/G polymorphism in exon 1 of the CTLA-4 gene and for the common mutant AIRE-1 allele (964de113) in United Kingdom subjects with APS1, by using the restriction enzymes Bst7II and BsrBI, respectively. There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD. In contrast, the mutant AIRE-1 964del13 allele was carried in one each of the 576 (0.2%) control subjects and the 90 (1.1%) AAD subjects as a heterozygote (P = 0.254, not significant), suggesting that this common AIRE-1 gene abnormality does not have a major role in sporadic (non-APS1) AAD.
authors.affiliation: Department of Medicine, University of Newcastle upon Tyne, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Vaidya
authors.forename: H
authors.initials: H
authors.lastname: Imrie
authors.forename: D R
authors.initials: DR
authors.lastname: Geatch
authors.forename: P
authors.initials: P
authors.lastname: Perros
authors.forename: S G
authors.initials: SG
authors.lastname: Ball
authors.forename: P H
authors.initials: PH
authors.lastname: Baylis
authors.forename: D
authors.initials: D
authors.lastname: Carr
authors.forename: S J
authors.initials: SJ
authors.lastname: Hurel
authors.forename: R A
authors.initials: RA
authors.lastname: James
authors.forename: W F
authors.initials: WF
authors.lastname: Kelly
authors.forename: E H
authors.initials: EH
authors.lastname: Kemp
authors.forename: E T
authors.initials: ET
authors.lastname: Young
authors.forename: A P
authors.initials: AP
authors.lastname: Weetman
authors.forename: P
authors.initials: P
authors.lastname: Kendall-Taylor
authors.forename: S H
authors.initials: SH
authors.lastname: Pearce
mesh_terms: D000069594:Abatacept; D000224:Addison Disease / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D014157:Transcription Factors; D000096927:AIRE Protein; C556706:CTLA4 protein, human