PMID- 23398374
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20221207
IS  - 1464-5491 (Electronic)
IS  - 0742-3071 (Print)
IS  - 0742-3071 (Linking)
VI  - 30
IP  - 6
DP  - 2013 Jun
TI  - HLA class II gene associations in African American type 1 diabetes reveal a 
      protective HLA-DRB1*03 haplotype.
PG  - 710-6
LID - 10.1111/dme.12148 [doi]
AB  - AIMS: Owing to strong linkage disequilibrium between markers, pinpointing disease 
      associations within genetic regions is difficult in European ancestral 
      populations, most notably the very strong association of the 
      HLA-DRB1*03-DQA1*05:01-DQB1*02:01 haplotype with Type 1 diabetes risk, which is 
      assumed to be because of a combination of HLA-DRB1 and HLA-DQB1. In contrast, 
      populations of African ancestry have greater haplotype diversity, offering the 
      possibility of narrowing down regions and strengthening support for a particular 
      gene in a region being causal. We aimed to study the human leukocyte antigen 
      (HLA) region in African American Type 1 diabetes. METHODS: Two hundred and 
      twenty-seven African American patients with Type 1 diabetes and 471 African 
      American control subjects were tested for association at the HLA class II genes, 
      HLA-DRB1, HLA-DQA1, HLA-DQB1 and 5147 single nucleotide polymorphisms across the 
      major histocompatibility complex region using logistic regression models. 
      Population admixture was accounted for with principal components analysis. 
      RESULTS: Single nucleotide polymorphism marker associations were explained by the 
      HLA associations, with the major peak over the class II loci. The HLA association 
      overall was extremely strong, as expected for Type 1 diabetes, even in African 
      Americans in whom diabetes diagnosis is heterogeneous. In addition, there were 
      unique features: the HLA-DRB1*03 haplotype was split into HLA-DRB1*03:01, which 
      confers greatest susceptibility in these samples (odds ratio 3.17, 95% CI 
      1.72-5.83) and HLA-DRB1*03:02, an allele rarely observed in Europeans, which 
      confers the greatest protection in these African American samples (odds ratio 
      0.22, 95% CI 0.09-0.55). CONCLUSIONS: The unique diversity of the African HLA 
      region we have uncovered supports a specific and major role for HLA-DRB1 in 
      HLA-DRB1*03 haplotype-associated Type 1 diabetes risk.
CI  - (c) 2013 The Authors. Diabetic Medicine (c) 2013 Diabetes UK.
FAU - Howson, J M M
AU  - Howson JM
AD  - JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Biomedical 
      Research Centre, Department of Medical Genetics, Cambridge Institute for Medical 
      Research, University of Cambridge, Cambridge, UK. jmmh2@medschl.cam.ac.uk
FAU - Roy, M S
AU  - Roy MS
FAU - Zeitels, L
AU  - Zeitels L
FAU - Stevens, H
AU  - Stevens H
FAU - Todd, J A
AU  - Todd JA
LA  - eng
GR  - 091157/Wellcome Trust/United Kingdom
GR  - 100140/Wellcome Trust/United Kingdom
GR  - MR/L003120/1/MRC_/Medical Research Council/United Kingdom
GR  - RG/08/014/24067/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130321
PL  - England
TA  - Diabet Med
JT  - Diabetic medicine : a journal of the British Diabetic Association
JID - 8500858
RN  - 0 (C-Peptide)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
SB  - IM
MH  - Adolescent
MH  - Black or African American
MH  - Alleles
MH  - C-Peptide/blood
MH  - Diabetes Mellitus, Type 1/*genetics/metabolism
MH  - Female
MH  - Gene Frequency
MH  - *Genes, MHC Class II
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA-DRB1 Chains/*genetics/metabolism
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Male
MH  - New Jersey
MH  - Oligonucleotide Array Sequence Analysis
MH  - *Polymorphism, Single Nucleotide
MH  - Principal Component Analysis
PMC - PMC3709123
EDAT- 2013/02/13 06:00
MHDA- 2013/11/05 06:00
CRDT- 2013/02/13 06:00
PHST- 2013/01/29 00:00 [received]
PHST- 2013/02/05 00:00 [accepted]
PHST- 2013/02/13 06:00 [entrez]
PHST- 2013/02/13 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
AID - 10.1111/dme.12148 [doi]
PST - ppublish
SO  - Diabet Med. 2013 Jun;30(6):710-6. doi: 10.1111/dme.12148. Epub 2013 Mar 21.