PMID- 30520966
OWN - NLM
STAT- MEDLINE
DCOM- 20200227
LR  - 20200227
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 104
IP  - 5
DP  - 2019 May 1
TI  - Sex Alters the MHC Class I HLA-A Association With Polyglandular Autoimmunity.
PG  - 1680-1686
LID - 10.1210/jc.2018-01974 [doi]
AB  - CONTEXT: The major histocompatibility complex (MHC) strongly contributes to the 
      development of polyglandular autoimmunity (PGA). OBJECTIVE: To evaluate the 
      impact of sex on human leukocyte antigen (HLA) association with PGA for the first 
      time. DESIGN: Cross-sectional immunogenetic study. SETTING: Academic tertiary 
      referral Orphan Disease Center for PGA (ORPHA 282196) and immunogenetics 
      laboratory. SUBJECTS: Patients (158) with coexistent type 1 diabetes and 
      autoimmune thyroid disease (adult type 3 PGA, ORPHA 227982) and 479 unrelated 
      healthy controls. INTERVENTIONS: All 637 white subjects were typed for HLA-A, -B, 
      -DRB1, -DQA1, and -DQB1 alleles at a two-field level. MAIN OUTCOME MEASURES: 
      Modification of the gene-disease association by sex. RESULTS: MHC class I HLA-A 
      association was sex related to both the total white adult type 3 PGA collective 
      (n = 158, P = 0.0065), as well as in PGA patients with autoimmune Hashimoto 
      thyroiditis (n = 91, P = 0.010). Compared with HLA-A*02:01, A*11:01 was 
      over-represented in male patients, yet under-represented in women (OR 1.49, 95% 
      CI 0.55 to 3.88 vs 0.42, 0.12 to 1.17). A*24:02 was under-represented in male but 
      not in female patients (OR 0.37, 95% CI 0.11 to 1.04 vs 1.19, 0.65 to 2.15). With 
      the exclusion of the five most frequent alleles (A*01:01, A*02:01, A*03:01, 
      A*11:01, and A*24:02), the sum of all other identified alleles was 
      under-represented in male patients (OR 0.37, 0.18 to 0.72, P = 0.0046). The 
      strong MHC HLA-B association with PGA (P < 0.0001) was not sex related (P = 
      0.55). Furthermore, no interaction with sex was observed for the MHC class II 
      HLA-DRB1, -DQA1, and -DQB1 alleles. CONCLUSION: MHC class I HLA-A association 
      with type 3 PGA is significantly affected by sex.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Flesch, Brigitte K
AU  - Flesch BK
AD  - Laboratory of Immunogenetics/HLA, German Red Cross Blood Service West, Bad 
      Kreuznach and Hagen, Germany.
FAU - Konig, Jochem
AU  - Konig J
AD  - Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes 
      Gutenberg University Medical Center, Mainz, Germany.
FAU - Frommer, Lara
AU  - Frommer L
AD  - Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical 
      Center, Mainz, Germany.
FAU - Hansen, Martin P
AU  - Hansen MP
AD  - Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical 
      Center, Mainz, Germany.
FAU - Kahaly, George J
AU  - Kahaly GJ
AD  - Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical 
      Center, Mainz, Germany.
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 (Biomarkers)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Biomarkers/*analysis
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 1/*genetics/immunology/pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-A Antigens/*genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Testing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polyendocrinopathies, Autoimmune/*genetics/immunology/pathology
MH  - Prognosis
MH  - Sex Factors
EDAT- 2018/12/07 06:00
MHDA- 2020/02/28 06:00
CRDT- 2018/12/07 06:00
PHST- 2018/09/12 00:00 [received]
PHST- 2018/11/30 00:00 [accepted]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2020/02/28 06:00 [medline]
PHST- 2018/12/07 06:00 [entrez]
AID - 5230932 [pii]
AID - 10.1210/jc.2018-01974 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2019 May 1;104(5):1680-1686. doi: 10.1210/jc.2018-01974.