PMID- 12050215
OWN - NLM
STAT- MEDLINE
DCOM- 20020703
LR  - 20231213
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 87
IP  - 6
DP  - 2002 Jun
TI  - AIRE mutations and human leukocyte antigen genotypes as determinants of the 
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype.
PG  - 2568-74
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, OMIM 
      240300) is a rare autoimmune disease caused by mutations in the autoimmune 
      regulator (AIRE) gene on chromosome 21q22.3. This monogenic disease provides an 
      interesting model for studies of other common and more complex autoimmune 
      diseases. The most common components of APECED are chronic mucocutaneous 
      candidiasis, hypoparathyroidism, and Addison's disease, but several other 
      endocrine deficiencies and ectodermal dystrophies also occur and the phenotype 
      varies widely. The AIRE genotype also varies; 42 different mutations have been 
      reported so far. To understand the complexity of the phenotype, we studied the 
      AIRE and human leukocyte antigen (HLA) class II genotypes in a series of patients 
      with APECED. The only association between the phenotype and the AIRE genotype was 
      the higher prevalence of candidiasis in the patients with the most common 
      mutation, R257X, than in those with other mutations. Addison's disease was 
      associated with HLA-DRB1*03 (P = 0.021), alopecia with HLA-DRB1*04- DQB1*0302 (P 
      < 0.001), whereas type 1 diabetes correlated negatively with 
      HLA-DRB1*15-DQB1*0602 (P = 0.036). The same HLA associations have previously been 
      established for non-APECED patients. We conclude that mutation of AIRE per se has 
      little influence on the APECED phenotype, whereas, in contrast to earlier 
      reports, HLA class II is a significant determinant.
FAU - Halonen, Maria
AU  - Halonen M
AD  - Department of Molecular Medicine, National Public Health Institute, Biomedicum, 
      Haartmaninkatu 8, FIN-00290 Helsinki, Finland. maria.halonen@ktl.fi
FAU - Eskelin, Petra
AU  - Eskelin P
FAU - Myhre, Anne-Grethe
AU  - Myhre AG
FAU - Perheentupa, Jaakko
AU  - Perheentupa J
FAU - Husebye, Eystein S
AU  - Husebye ES
FAU - Kampe, Olle
AU  - Kampe O
FAU - Rorsman, Fredrik
AU  - Rorsman F
FAU - Peltonen, Leena
AU  - Peltonen L
FAU - Ulmanen, Ismo
AU  - Ulmanen I
FAU - Partanen, Jukka
AU  - Partanen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Autoantibodies/analysis
MH  - Child
MH  - Genotype
MH  - HLA-DQ Antigens/analysis
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/analysis/immunology
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Middle Aged
MH  - *Mutation
MH  - Phenotype
MH  - Polyendocrinopathies, Autoimmune/*genetics/immunology
MH  - Transcription Factors/*genetics
MH  - AIRE Protein
EDAT- 2002/06/07 10:00
MHDA- 2002/07/04 10:01
CRDT- 2002/06/07 10:00
PHST- 2002/06/07 10:00 [pubmed]
PHST- 2002/07/04 10:01 [medline]
PHST- 2002/06/07 10:00 [entrez]
AID - 10.1210/jcem.87.6.8564 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2002 Jun;87(6):2568-74. doi: 10.1210/jcem.87.6.8564.