PMID- 11994372
OWN - NLM
STAT- MEDLINE
DCOM- 20020614
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 87
IP  - 5
DP  - 2002 May
TI  - The Karlsburg type 1 diabetes risk study of a normal schoolchild population: 
      association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles 
      in antibody-positive individuals.
PG  - 2254-61
AB  - The intent of this study was to analyze the prevalence of diabetes-associated 
      autoantibodies (AAbs) at or above the 99(th) percentile as well as their 
      association with human leukocyte antigen (HLA)-DQB1 alleles in a normal 
      population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase 
      (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by 
      (125)I-antigen binding and islet cell antibodies (ICA) immunohistochemically in 
      181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children 
      and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one 
      AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P < 
      0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the 
      diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001-0.006) as well 
      as a decreased frequency in the protective allele *0602 (P < 0.001-0.022). 
      DQB1*0602 was completely absent within children with multiple AAbs or with GADA, 
      IA2-A, or IAA at or above the 99.9(th) percentile. In comparison to children with 
      single AAbs, the frequency of associated/protective alleles of children with 
      multiple AAbs was enhanced/diminished (P = 0.004-0.009). The study shows that 
      also in the general population the multiple AAbs or high level single AAbs 
      predict rather certainly a HLA-DQB1-mediated diabetes susceptibility as shown for 
      first degree relatives of type 1 diabetic patients.
FAU - Schlosser, Michael
AU  - Schlosser M
AD  - Institute of Pathophysiology, Ernst Moritz Arndt University of Greifswald, 
      Karlsburg D-17495, Germany.
FAU - Strebelow, Martina
AU  - Strebelow M
FAU - Wassmuth, Ralf
AU  - Wassmuth R
FAU - Arnold, Marie-Luise
AU  - Arnold ML
FAU - Breunig, Isabel
AU  - Breunig I
FAU - Rjasanowski, Ilona
AU  - Rjasanowski I
FAU - Ziegler, Brigitte
AU  - Ziegler B
FAU - Ziegler, Manfred
AU  - Ziegler M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Adult
MH  - *Alleles
MH  - Autoantibodies/*analysis
MH  - Child
MH  - Diabetes Mellitus, Type 1/etiology/*genetics/*immunology
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Predictive Value of Tests
MH  - Reference Values
MH  - Risk Factors
EDAT- 2002/05/08 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/05/08 10:00
PHST- 2002/05/08 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/05/08 10:00 [entrez]
AID - 10.1210/jcem.87.5.8491 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2002 May;87(5):2254-61. doi: 10.1210/jcem.87.5.8491.