PMID- 16464953
OWN - NLM
STAT- MEDLINE
DCOM- 20060607
LR  - 20180905
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 91
IP  - 5
DP  - 2006 May
TI  - Specific human leukocyte antigen DQ influence on expression of antiislet 
      autoantibodies and progression to type 1 diabetes.
PG  - 1705-13
AB  - CONTEXT: Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic 
      association with type 1 diabetes (T1DM) risk. OBJECTIVE: The objective of the 
      study was to analyze whether HLA DQ alleles influence the development of 
      antiislet autoantibodies, the progression to T1DM among autoantibody-positive 
      relatives, or both. DESIGN: The Diabetes Prevention Trial-1 screened more than 
      90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody 
      (ICA) expression between 1994 and 2002. SETTING: The study was conducted in the 
      general community. PARTICIPANTS: The Diabetes Prevention Trial-1 found 2817 
      ICA-positive relatives who were tested for biochemical autoantibodies (GAD65, 
      ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for 
      progression to diabetes for up to 8 yr (median, 3.6 yr). MAIN OUTCOME MEASURE: 
      Progression to T1DM was measured. RESULTS: High-risk DQ haplotypes and genotypes 
      were associated with a higher percentage of relatives expressing multiple 
      biochemical autoantibodies and higher T1DM risk (e.g., respectively, 59 and 36% 
      at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype). 
      The number of autoantibodies expressed significantly increased T1DM risk and 
      across different DQ genotypes, autoantibody positivity directly correlated with 
      diabetes risk. However, multivariate analyses indicated that the influence of 
      most genotypes on T1DM risk was not independent from autoantibody expression, 
      with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic 
      combinations conferred 5-yr diabetes risks significantly lower (e.g. 
      7%-DQA1*0201-DQB1*0201/DQA1*0501-DQB1*0201 and 
      14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201) than when those haplotypes were 
      found in other combinations. CONCLUSION: HLA DQ alleles determine autoantibody 
      expression, which is correlated with diabetes progression. Among 
      autoantibody-positive relatives, most HLA DQ genotypes did not further influence 
      T1DM risk.
FAU - Redondo, Maria J
AU  - Redondo MJ
AD  - Department of Endocrinology, University Clinic of Navarra, 31008 Pamplona, Spain.
FAU - Babu, Sunanda
AU  - Babu S
FAU - Zeidler, Adina
AU  - Zeidler A
FAU - Orban, Tihamer
AU  - Orban T
FAU - Yu, Liping
AU  - Yu L
FAU - Greenbaum, Carla
AU  - Greenbaum C
FAU - Palmer, Jerry P
AU  - Palmer JP
FAU - Cuthbertson, David
AU  - Cuthbertson D
FAU - Eisenbarth, George S
AU  - Eisenbarth GS
FAU - Krischer, Jeffrey P
AU  - Krischer JP
FAU - Schatz, Desmond
AU  - Schatz D
CN  - Diabetes Prevention Trial Type 1 Study Group
LA  - eng
GR  - 5R37DK32083/DK/NIDDK NIH HHS/United States
GR  - N01RR00037/RR/NCRR NIH HHS/United States
GR  - R01A139213/PHS HHS/United States
GR  - M01RR00069/RR/NCRR NIH HHS/United States
GR  - R01 A1 4431-03/PHS HHS/United States
GR  - UC4 DK117009/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060207
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)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Autoantibodies/*biosynthesis
MH  - Child
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Diabetes Mellitus, Type 1/*genetics/*pathology
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - HLA-DQ Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Life Tables
MH  - Male
MH  - Survival Analysis
EDAT- 2006/02/09 09:00
MHDA- 2006/06/08 09:00
CRDT- 2006/02/09 09:00
PHST- 2006/02/09 09:00 [pubmed]
PHST- 2006/06/08 09:00 [medline]
PHST- 2006/02/09 09:00 [entrez]
AID - jc.2005-1695 [pii]
AID - 10.1210/jc.2005-1695 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2006 May;91(5):1705-13. doi: 10.1210/jc.2005-1695. Epub 
      2006 Feb 7.