PMID- 15292346
OWN - NLM
STAT- MEDLINE
DCOM- 20040903
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 89
IP  - 8
DP  - 2004 Aug
TI  - Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte 
      antigen class II genotype: a population-based study in the United Kingdom.
PG  - 4037-43
AB  - The autoimmune disease process leading to childhood-onset type 1 diabetes appears 
      to start in infancy, and decisions on treatment to prevent initiation of 
      autoimmunity will need to be based on genetic susceptibility alone. We set out to 
      quantify the absolute risk associated with human leukocyte antigen (HLA) 
      DRB1-DQA1-DQB1 class II genotypes and to develop strategies for recruitment into 
      primary prevention trials. HLA class II haplotype- and genotype-specific risks 
      were derived from 753 United Kingdom families from the Bart's-Oxford 
      population-based study of type 1 diabetes and combined with incidence data from 
      the region to calculate the absolute risk of development of diabetes. A hierarchy 
      of susceptibility was established for both HLA class II haplotypes and genotypes, 
      and the sensitivity and specificity of each genotype was established relative to 
      age at disease onset. Highest risk was conferred by the genotype 
      DRB1*03-DQA1*0501-DQB1*0201/DRB1*0401-DQA1*0301-DQB1*0302 (5% absolute risk of 
      diabetes by age 15 yr), although sensitivity was only 22.6%. Combining the six 
      highest risk genotypes conferred similar risk but increased sensitivity to 36.6% 
      and was most sensitive for diagnosis of diabetes before age 5 yr (48.4%), whereas 
      inclusion of 11 genotypes achieved the same sensitivity for diagnosis for ages 
      10-14 yr. Analysis of genotype-specific risk should form the basis for design of 
      future primary prevention trials in the general population.
FAU - Lambert, A Paul
AU  - Lambert AP
AD  - Division of Medicine, University of Bristol, Bristol BS10 5NB, United Kingdom.
FAU - Gillespie, Kathleen M
AU  - Gillespie KM
FAU - Thomson, Glenys
AU  - Thomson G
FAU - Cordell, Heather J
AU  - Cordell HJ
FAU - Todd, John A
AU  - Todd JA
FAU - Gale, Edwin A M
AU  - Gale EA
FAU - Bingley, Polly J
AU  - Bingley PJ
LA  - eng
GR  - GM35326/GM/NIGMS 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 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*04:01 antigen)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Age of Onset
MH  - Diabetes Mellitus, Type 1/*epidemiology/*genetics/immunology
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DQ Antigens/genetics
MH  - HLA-DQ alpha-Chains
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Prospective Studies
MH  - ROC Curve
MH  - Risk Assessment
EDAT- 2004/08/05 05:00
MHDA- 2004/09/04 05:00
CRDT- 2004/08/05 05:00
PHST- 2004/08/05 05:00 [pubmed]
PHST- 2004/09/04 05:00 [medline]
PHST- 2004/08/05 05:00 [entrez]
AID - 89/8/4037 [pii]
AID - 10.1210/jc.2003-032084 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2004 Aug;89(8):4037-43. doi: 10.1210/jc.2003-032084.