PMID- 27411431
OWN - NLM
STAT- MEDLINE
DCOM- 20170328
LR  - 20210503
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 17 Suppl 22
DP  - 2016 Jul
TI  - Genetic susceptibility to type 1 diabetes in childhood - estimation of HLA class 
      II associated disease risk and class II effect in various phases of islet 
      autoimmunity.
PG  - 8-16
LID - 10.1111/pedi.12327 [doi]
AB  - OBJECTIVE: The HLA-DR/DQ region remains the major determinant of susceptibility 
      to type 1 diabetes (T1D) despite the more than 50 risk affecting loci outside 
      human leukocyte antigen (HLA) region that have been identified. We aimed at 
      developing a simple risk estimation based on HLA class II genotyping, which was 
      also tested by analyzing HLA class II effect on the autoantibody seroconversion 
      and further progression to diabetes. SUBJECTS AND METHODS: A total of 2991 trio 
      families with a diabetic child from the Finnish Pediatric Diabetes Register were 
      genotyped and the risk contributed by each DR-DQ haplotype calculated through 
      transmission analysis. The genotype risk was estimated based on the summary 
      effect of haplotypes. Genotype grouping was further tested in a subcohort of the 
      Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study RESULTS: The 
      summary effect of haplotypes was generally seen in genotypes, while the expected 
      synergistic effect of DR3-DQ2 and DR4-DQ8 (DRB1*04:03 excluded) combination was 
      also clear in the T1D risk association analysis. This highest risk DR/DQ genotype 
      was found in 21.6% of patients and 2.0% of controls, odds ratio (OR) = 13.2 
      (10.1-17.2), whereas the lowest risk genotype contained only 0.8% of patients and 
      28.0% of controls, OR = 0.02 (0.01-0.03). In the subcohort from the DIPP study 
      the risk grades correlated clearly with seroconversion for islet autoantibodies 
      and T1D development. In contrast, DR/DQ risk groups did not associate with the 
      progression rate from advanced autoimmunity to clinical diabetes. CONCLUSIONS: 
      Class II HLA genotype groups improve the estimation of T1D risk. Class II effect 
      is limited to the early phase of the disease process characterized by 
      seroconversion for islet autoantibodies.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Ilonen, J
AU  - Ilonen J
AD  - Immunogenetics Laboratory, University of Turku, Turku, Finland.
FAU - Kiviniemi, M
AU  - Kiviniemi M
AD  - Immunogenetics Laboratory, University of Turku, Turku, Finland.
FAU - Lempainen, J
AU  - Lempainen J
AD  - Immunogenetics Laboratory, University of Turku, Turku, Finland.
FAU - Simell, O
AU  - Simell O
AD  - Department of Pediatrics, University of Turku, Turku, Finland.
AD  - Department of Pediatrics, Turku University Hospital, Turku, Finland.
FAU - Toppari, J
AU  - Toppari J
AD  - Department of Pediatrics, University of Turku, Turku, Finland.
AD  - Department of Pediatrics, Turku University Hospital, Turku, Finland.
AD  - Department of Physiology, University of Turku, Turku, Finland.
FAU - Veijola, R
AU  - Veijola R
AD  - Department of Pediatrics, University of Oulu, PEDEGO Research Unit, MRC Oulu, 
      Oulu, Finland.
AD  - Department of Pediatrics, Oulu University Hospital, Oulu, Finland.
FAU - Knip, M
AU  - Knip M
AD  - Children's Hospital, University of Helsinki and Helsinki University Hospital, 
      Helsinki, Finland, Research Programs Unit, Diabetes and Obesity, University of 
      Helsinki, Helsinki, Finland.
AD  - Folkhalsan Research Center, Helsinki, Finland.
AD  - Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
CN  - Finnish Pediatric Diabetes Register
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
SB  - IM
MH  - Adult
MH  - Autoimmunity
MH  - Case-Control Studies
MH  - Child
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - *Genes, MHC Class II
MH  - Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - Islets of Langerhans/immunology
MH  - Male
MH  - Risk Assessment
OTO - NOTNLM
OT  - HLA class II
OT  - genetics
OT  - islet autoimmunity
OT  - type 1 diabetes
EDAT- 2016/07/15 06:00
MHDA- 2017/03/30 06:00
CRDT- 2016/07/15 06:00
PHST- 2015/08/13 00:00 [received]
PHST- 2015/09/10 00:00 [revised]
PHST- 2015/09/17 00:00 [accepted]
PHST- 2016/07/15 06:00 [entrez]
PHST- 2016/07/15 06:00 [pubmed]
PHST- 2017/03/30 06:00 [medline]
AID - 10.1111/pedi.12327 [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2016 Jul;17 Suppl 22:8-16. doi: 10.1111/pedi.12327.