PMID- 23721563
OWN - NLM
STAT- MEDLINE
DCOM- 20140609
LR  - 20131029
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 14
IP  - 7
DP  - 2013 Nov
TI  - Associations of polymorphisms in non-HLA loci with autoantibodies at the 
      diagnosis of type 1 diabetes: INS and IKZF4 associate with insulin 
      autoantibodies.
PG  - 490-6
LID - 10.1111/pedi.12046 [doi]
AB  - OBJECTIVE: More than 50 loci outside the human leukocyte antigen (HLA) region 
      have been confirmed to affect type 1 diabetes (T1D) risk but their effect on 
      beta-cell autoimmunity is poorly defined. We analyzed the association of 35 single 
      nucleotide polymorphism (SNP) markers previously associated with T1D with the 
      presence of disease-predictive autoantibodies at the time of T1D diagnosis. 
      SUBJECTS AND METHODS: The study cohort comprised 1554 children diagnosed with T1D 
      before the age of 15 yr. The associations between various genotypes and 
      positivity for antibodies against islet cells [islet cell antibodies (ICA)], 
      insulin [insulin autoantibodies (IAA)], glutamic acid decarboxylase (GADA), islet 
      antigen 2 (IA2A), and zinc transporter 8 (ZnT8A) were analyzed. RESULTS: INS gene 
      polymorphism rs689 and IKZF4 polymorphism (rs1701704) were strongly associated 
      with IAA positivity at the time of T1D diagnosis (p = 0.000004 and 0.00044, 
      respectively). The presence of the T1D-risk conferring INS AA genotype was 
      associated with IAA. In contrast, the presence of the susceptible C allele of the 
      IKZF4 marker was inversely associated with IAA. The INS and IKZF4 polymorphisms 
      were not significantly associated with ICA, GADA, IA2A, or ZnT8A positivity. 
      CONCLUSIONS: Both INS and IKZF4 polymorphisms modified the probability of IAA 
      positivity at time of T1D onset but the inverse association of IKZF4 risk allele 
      with IAA suggests that the IKZF4 polymorphism is involved in a pathway of beta-cell 
      autoimmunity alternate to the route characterized by IAA and development of T1D 
      in early childhood. The IKZF4 gene encodes Eos, which is implicated to play an 
      important role in Treg programming where this gene might exert its influence on 
      T1D risk.
CI  - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Lempainen, J
AU  - Lempainen J
AD  - Immunogenetics Laboratory, University of Turku, Turku, Finland; Department of 
      Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
FAU - Harkonen, T
AU  - Harkonen T
FAU - Laine, Ap
AU  - Laine A
FAU - Knip, M
AU  - Knip M
FAU - Ilonen, J
AU  - Ilonen J
CN  - Finnish Pediatric Diabetes Register
LA  - eng
PT  - Journal Article
DEP - 20130531
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Autoantibodies)
RN  - 0 (IKZF4 protein, human)
RN  - 0 (Insulin Antibodies)
RN  - 0 (islet cell antibody)
RN  - 148971-36-2 (Ikaros Transcription Factor)
SB  - IM
MH  - Adolescent
MH  - Autoantibodies/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - Humans
MH  - Ikaros Transcription Factor/*genetics
MH  - Infant
MH  - Insulin Antibodies/*genetics/immunology
MH  - Islets of Langerhans/immunology
MH  - Male
MH  - Polymorphism, Single Nucleotide
OTO - NOTNLM
OT  - IKZF4
OT  - INS
OT  - insulin autoantibodies
OT  - single nucleotide polymorphism
OT  - type 1 diabetes
FIR - Knip, Mikael
IR  - Knip M
FIR - Groop, Per-Henrik
IR  - Groop PH
FIR - Ilonen, Jorma
IR  - Ilonen J
FIR - Lappi, Anneli
IR  - Lappi A
FIR - Otonkoski, Timo
IR  - Otonkoski T
FIR - Saha, Marja-Terttu
IR  - Saha MT
FIR - Simell, Olli
IR  - Simell O
FIR - Talvitie, Timo
IR  - Talvitie T
FIR - Vaarala, Outi
IR  - Vaarala O
FIR - Veijola, Riitta
IR  - Veijola R
FIR - Aito, Henrikka
IR  - Aito H
FIR - Bondestam, Jonas
IR  - Bondestam J
FIR - Dahllund, Thomas
IR  - Dahllund T
FIR - Granvik, Johanna
IR  - Granvik J
FIR - Haapalehto-Ikonen, Maarit
IR  - Haapalehto-Ikonen M
FIR - Hamalainen, Anu-Maaria
IR  - Hamalainen AM
FIR - Huopio, Hanna
IR  - Huopio H
FIR - Johansson, Christian
IR  - Johansson C
FIR - Kinnala, Anne
IR  - Kinnala A
FIR - Korhonen, Jussi
IR  - Korhonen J
FIR - Lautala, Pentti
IR  - Lautala P
FIR - Lindstr, Kaija
IR  - Lindstr K
FIR - Miettinen, Paivi
IR  - Miettinen P
FIR - Mustila, Taina
IR  - Mustila T
FIR - Nuuja, Anja
IR  - Nuuja A
FIR - Nykanen, Paivi
IR  - Nykanen P
FIR - Ojanpera, Jussi
IR  - Ojanpera J
FIR - Anne-Putto-Laurila
IR  - Anne-Putto-Laurila
FIR - Saha, Marja-Terttu
IR  - Saha MT
FIR - Sankila, Juhani
IR  - Sankila J
FIR - Suomi, Anne-Maarit
IR  - Suomi AM
FIR - Tenhola, Sirpa
IR  - Tenhola S
FIR - Varimo, Pentti
IR  - Varimo P
FIR - Veijola, Riitta
IR  - Veijola R
FIR - Virransalo, Ritva
IR  - Virransalo R
FIR - Vuolukka, Pentti
IR  - Vuolukka P
FIR - Vuorela, Niina
IR  - Vuorela N
FIR - Ylitalo, Samuli
IR  - Ylitalo S
EDAT- 2013/06/01 06:00
MHDA- 2014/06/10 06:00
CRDT- 2013/06/01 06:00
PHST- 2013/02/04 00:00 [received]
PHST- 2013/03/17 00:00 [revised]
PHST- 2013/04/04 00:00 [accepted]
PHST- 2013/06/01 06:00 [entrez]
PHST- 2013/06/01 06:00 [pubmed]
PHST- 2014/06/10 06:00 [medline]
AID - 10.1111/pedi.12046 [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2013 Nov;14(7):490-6. doi: 10.1111/pedi.12046. Epub 2013 May 
      31.