PMID- 10323407
OWN - NLM
STAT- MEDLINE
DCOM- 19990527
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 5
DP  - 1999 May
TI  - Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 
      allele in unaffected, islet cell antibody-positive first degree relatives and in 
      rare patients with type 1 diabetes.
PG  - 1722-8
AB  - The human leukocyte antigen (HLA)-DQA1*0102/DQB1*0602/DRB1*1501 (DR2) haplotype 
      confers strong protection from type 1 diabetes. Growing evidence suggests that 
      such protection may be mostly encoded by the DQB1*0602 allele, and we reported 
      that even first degree relatives with islet cell antibodies (ICA) have an 
      extremely low diabetes risk if they carry DQB1*0602. Recently, novel variants of 
      the DQB1*0602 and *0603 alleles were reported in four patients with type 1 
      diabetes originally typed as DQB1*0602 with conventional techniques. One 
      inference from this observation is that DQB1*0602 may confer absolute protection 
      and may never occur in type 1 diabetes. By this hypothesis, all patients typed as 
      DQB1*0602 positive with conventional techniques should carry one of the above 
      diabetes-permissive variants instead of the protective DQB1*0602. Such variants 
      could also occur in ICA/DQB1*0602-positive relatives, with the implication that 
      their diabetes risk could be significantly higher than previously estimated. We 
      therefore sequenced the DQB1*0602 and DQA1*0102 alleles in all 
      ICA/DQB1*0602-positive relatives (n = 8) previously described and in six rare 
      patients with type 1 diabetes and DQB1*0602. We found that all relatives and 
      patients carry the known DQB1*0602 and DQA1*0102 sequences, and none of them has 
      the mtDNA A3243G mutation associated with late-onset diabetes in ICA-positive 
      individuals. These findings suggest that diabetes-permissive DQB1*0602/3 variants 
      may be very rare. Thus, although the protective effect associated with DQB1*0602 
      is extremely powerful, it is not absolute. Nonetheless, the development of 
      diabetes in individuals with DQB1*0602 remains extremely unlikely, even in the 
      presence of ICA, as confirmed by our further evaluation of ICA/DQB1*0602-positive 
      relatives, none of whom has yet developed diabetes.
FAU - Pugliese, A
AU  - Pugliese A
AD  - Diabetes Research Institute, University of Miami School of Medicine, Florida 
      33136, USA. apuglies@mednet.med.miami.edu
FAU - Kawasaki, E
AU  - Kawasaki E
FAU - Zeller, M
AU  - Zeller M
FAU - Yu, L
AU  - Yu L
FAU - Babu, S
AU  - Babu S
FAU - Solimena, M
AU  - Solimena M
FAU - Moraes, C T
AU  - Moraes CT
FAU - Pietropaolo, M
AU  - Pietropaolo M
FAU - Friday, R P
AU  - Friday RP
FAU - Trucco, M
AU  - Trucco M
FAU - Ricordi, C
AU  - Ricordi C
FAU - Allen, M
AU  - Allen M
FAU - Noble, J A
AU  - Noble JA
FAU - Erlich, H A
AU  - Erlich HA
FAU - Eisenbarth, G S
AU  - Eisenbarth GS
LA  - eng
GR  - DK32083/DK/NIDDK NIH HHS/United States
GR  - MO1RR00069/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (islet cell antibody)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Autoantibodies/analysis/*genetics
MH  - Base Sequence
MH  - DNA, Mitochondrial/analysis/genetics
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - Follow-Up Studies
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Molecular Sequence Data
MH  - Mutation
EDAT- 1999/05/14 00:00
MHDA- 1999/05/14 00:01
CRDT- 1999/05/14 00:00
PHST- 1999/05/14 00:00 [pubmed]
PHST- 1999/05/14 00:01 [medline]
PHST- 1999/05/14 00:00 [entrez]
AID - 10.1210/jcem.84.5.5684 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 May;84(5):1722-8. doi: 10.1210/jcem.84.5.5684.