PMID- 24187405
OWN - NLM
STAT- MEDLINE
DCOM- 20140312
LR  - 20140103
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 99
IP  - 1
DP  - 2014 Jan
TI  - HLA class II haplotypes differentiate between the adult autoimmune polyglandular 
      syndrome types II and III.
PG  - E177-82
LID - 10.1210/jc.2013-2852 [doi]
AB  - BACKGROUND: Genetics of the adult autoimmune polyglandular syndrome (APS) is 
      poorly understood. AIM: The aim of this study was to gain further insight into 
      the genetics of the adult APS types. SITE: The study was conducted at a 
      university referral center. METHODS: The human leukocyte antigen (HLA) class II 
      alleles, haplotypes, and genotypes were determined in a large cohort of patients 
      with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy 
      controls by the consistent application of high-resolution typing at a four-digit 
      level. RESULTS: Comparison of the allele and haplotype frequencies significantly 
      discriminated patients with APS vs AITD and controls. The HLA class II alleles 
      DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more 
      frequently (P<.001) in APS than in AITD and controls, whereas the alleles 
      DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc<.001) 
      and controls (Pc<.01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 
      (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were 
      overrepresented in APS (Pc<.001). Combination of both haplotypes to a genotype 
      was highly prevalent in APS vs AITD and controls (Pc<.001). Dividing the APS 
      collective into those with Addison's disease (APS type II) and those without 
      Addison's disease but including type 1 diabetes and AITD (APS type III) 
      demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III 
      (Pc<.001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II 
      (Pc<.001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and 
      DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II 
      (Pc<.01). CONCLUSIONS: HLA class II haplotypes differentiate between the adult 
      APS types II and III. Susceptible haplotypes favor the development of 
      polyglandular autoimmunity in patients with AITD.
FAU - Flesch, B K
AU  - Flesch BK
AD  - Laboratory of Immunogenetics/HLA (B.K.F., C.W.), German Red Cross Blood Service 
      West, Bad Kreuznach 55543, Germany; Molecular Thyroid Research Laboratory (N.M., 
      G.J.K.), Johannes Gutenberg University Medical Center, Mainz 55101, Germany; 
      Bioinformatics Unit (T.A.) and Center for Transfusion Medicine (J.B.), German Red 
      Cross Blood Service West, Hagen 58097, Germany.
FAU - Matheis, N
AU  - Matheis N
FAU - Alt, T
AU  - Alt T
FAU - Weinstock, C
AU  - Weinstock C
FAU - Bux, J
AU  - Bux J
FAU - Kahaly, G J
AU  - Kahaly GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131220
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Case-Control Studies
MH  - Child
MH  - Diagnosis, Differential
MH  - Female
MH  - Gene Frequency
MH  - *Genes, MHC Class II
MH  - *Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polyendocrinopathies, Autoimmune/classification/*diagnosis/genetics
MH  - Young Adult
EDAT- 2013/11/05 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - jc.2013-2852 [pii]
AID - 10.1210/jc.2013-2852 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2014 Jan;99(1):E177-82. doi: 10.1210/jc.2013-2852. Epub 
      2013 Dec 20.