PMID- 21744463
OWN - NLM
STAT- MEDLINE
DCOM- 20111031
LR  - 20211020
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Print)
IS  - 1520-7552 (Linking)
VI  - 27
IP  - 5
DP  - 2011 Jul
TI  - Predictors of associated autoimmune diseases in families with type 1 diabetes: 
      results from the Type 1 Diabetes Genetics Consortium.
PG  - 493-8
LID - 10.1002/dmrr.1189 [doi]
AB  - BACKGROUND: Type 1 diabetes (T1D) is a clinically heterogeneous disease. The 
      presence of associated autoimmune diseases (AAIDs) may represent a distinct form 
      of autoimmune diabetes, with involvement of specific mechanisms. The aim of this 
      study was to find predictors of AAIDs in the Type 1 Diabetes Genetics Consortium 
      data set. METHODS: Three thousand two hundred and sixty-three families with at 
      least two siblings with T1D were included. Clinical information was obtained 
      using questionnaires, anti-GAD (glutamic acid decarboxylase) and anti-protein 
      tyrosine phosphatase (IA-2) were measured and human leukocyte antigen (HLA) 
      genotyping was performed. Siblings with T1D with and without AAIDs were compared 
      and a multivariate regression analysis was performed to find predictors of AAIDs. 
      T1D-associated HLA haplotypes were defined as the four most susceptible and 
      protective, respectively. RESULTS: One or more AAIDs were present in 14.4% of the 
      T1D affected siblings. Age of diabetes onset, current age and time since 
      diagnosis were higher, there was a female predominance and more family history of 
      AAIDs in the group with AAIDs, as well as more frequent anti-GAD and less 
      frequent anti-IA-2 antibodies. Risk and protective HLA haplotype distributions 
      were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group 
      with AAIDs. In the multivariate analysis, female gender, age of onset, family 
      history of AAID, time since diagnosis and anti-GAD positivity were significantly 
      associated with AAIDs. CONCLUSIONS: In patients with T1D, the presence of AAIDs 
      is associated with female predominance, more frequent family history of AAIDs, 
      later onset of T1D and more anti-GAD antibodies, despite longer duration of the 
      disease. The predominance of certain HLA haplotypes suggests that specific 
      mechanisms of disease may be involved.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Wagner, Ana M
AU  - Wagner AM
AD  - Endocrinology Department, Complejo Hospitalario Universitario Insular-Materno 
      Infantil, de Gran Canaria, Spain. awagner@dcmq.ulpgc.es
FAU - Santana, Angelo
AU  - Santana A
FAU - Hernndez, Marta
AU  - Hernndez M
FAU - Wiebe, Julia C
AU  - Wiebe JC
FAU - Novoa, Javier
AU  - Novoa J
FAU - Mauricio, Didac
AU  - Mauricio D
CN  - T1DGC6
LA  - eng
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
GR  - U01 DK062418-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Antibodies)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Antibodies/analysis
MH  - Autoimmune Diseases/*genetics/immunology
MH  - Child
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Family Health
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Glutamate Decarboxylase/immunology
MH  - HLA-DQ Antigens/analysis
MH  - HLA-DR Antigens/analysis
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Protein Tyrosine Phosphatases/immunology
PMC - PMC3137249
MID - NIHMS287831
COIS- Conflict of interest The authors are not aware of any conflict of interest 
      regarding the contents of this manuscript.
EDAT- 2011/07/12 06:00
MHDA- 2011/11/01 06:00
PMCR- 2012/07/01
CRDT- 2011/07/12 06:00
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/11/01 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - 10.1002/dmrr.1189 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2011 Jul;27(5):493-8. doi: 10.1002/dmrr.1189.