PMID- 10084595
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 3
DP  - 1999 Mar
TI  - Human leukocyte antigen-DQB1* genotypes encoding aspartate at position 57 are 
      associated with 3beta-hydroxysteroid dehydrogenase autoimmunity in premature 
      ovarian failure.
PG  - 1056-60
AB  - Premature ovarian failure (POF) has an autoimmune pathogenesis in a significant 
      proportion of cases. Autoantibodies to the steroid cell enzyme, 
      3beta-hydroxysteroid dehydrogenase (3betaHSD) are present in one fifth of 
      patients and may identify an autoimmune subgroup. As autoimmune diseases are 
      associated with alleles of the human leukocyte antigen (HLA) genes, we examined 
      the distribution of HLA-DRB1 and -DQB1 genotypes in 118 women with POF, of whom 
      21% had 3betaHSD autoantibodies, and 134 racially matched control subjects. Two 
      HLA-DQB1 alleles, 0301 and 0603, were associated with 3betaHSD autoantibody 
      positivity (P = 0.04 and P = 0.006, respectively). As the DQB1*0301 and -0603 
      genes share an identical codon at position 57 (aspartate, Asp), we analyzed the 
      frequency of DQbeta-Asp57 encoding DQB1 genes in our series. Eighteen of 21 POF 
      patients with 3betaHSD autoantibodies had DQbeta-Asp57-encoding genotypes 
      (haplotype frequency, 27 of 42; 64%) compared with 92 of 134 control subjects 
      (haplotype frequency, 109 of 268; 41%; P = 0.004), and 9 of 21 (43%) cases were 
      homozygous for codon 57 genotypes compared with 17 of 134 (13%) control subjects 
      (P = 0.0006). These probability values were not significant after correction for 
      multiple testing, and these trends will therefore require confirmation in larger 
      cohorts. HLA class II molecules present antigenic peptides to CD4+ T lymphocytes. 
      DQbeta57 occupies a key site at the boundary of the peptide binding groove, with 
      a major impact on peptide binding. Our preliminary demonstration of an 
      association between POF, 3betaHSD autoimmunity, and a distinctive HLA-DQ molecule 
      supports the hypothesis that autoantibodies to this steroid cell enzyme may be 
      markers of autoimmune ovarian failure and suggests that presentation of 
      autoantigenic or external peptides to T lymphocytes by HLA-DQ molecules with 
      Asp57-beta-chains is important in the pathogenesis of this disease.
FAU - Arif, S
AU  - Arif S
AD  - Department of Immunology, King's College School of Medicine and Dentistry, 
      London, United Kingdom.
FAU - Underhill, J A
AU  - Underhill JA
FAU - Donaldson, P
AU  - Donaldson P
FAU - Conway, G S
AU  - Conway GS
FAU - Peakman, M
AU  - Peakman M
LA  - eng
PT  - Journal Article
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  - 30KYC7MIAI (Aspartic Acid)
RN  - 9010-34-8 (Thyroglobulin)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/*immunology
MH  - Amino Acid Sequence/genetics
MH  - Aspartic Acid/*genetics
MH  - Autoantibodies/analysis
MH  - Autoimmunity/*genetics/immunology
MH  - Female
MH  - Genotype
MH  - HLA-DQ Antigens/analysis/*genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/analysis
MH  - Humans
MH  - Primary Ovarian Insufficiency/*genetics/*immunology
MH  - Thyroglobulin/immunology
MH  - Thyroid Gland/immunology
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1210/jcem.84.3.5556 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Mar;84(3):1056-60. doi: 10.1210/jcem.84.3.5556.