PMID- 20445565
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20211020
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 11
IP  - 5
DP  - 2010 Jul
TI  - The association between the PTPN22 1858C>T variant and type 1 diabetes depends on 
      HLA risk and GAD65 autoantibodies.
PG  - 406-15
LID - 10.1038/gene.2010.12 [doi]
AB  - The single nucleotide polymorphism 1858C>T in the PTPN22 gene is associated with 
      type 1 diabetes (T1D) in several populations. Earlier reports have suggested that 
      the association may be modified by human leukocyte antigen (HLA), as well as by 
      islet autoantibodies. In a large case-control study of Swedish incident T1D 
      patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) 
      measure of association was dependent on HLA or autoantibodies against the islet 
      autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, 
      islet antigen-2, or islet cell. The association between the carrier status of 
      1858C>T allele in PTPN22 (PTPN22(CT+TT)) and T1D was modified by HLA. In 
      addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in 
      GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison=0.007). The OR 
      of association between PTPN22(CT+TT) and GADA-positive T1D declined with 
      increasing HLA-risk category from 6.12 to 1.54 (P=0.003); no such change was 
      detected in GADA-negative T1D (P=0.722) (P for comparison=0.001). However, the 
      absolute difference in risk between PTPN22(CC) and PTPN22(CT+TT) subjects with 
      high-risk HLA was five times higher than that for subjects with low-risk HLA. We 
      hypothesize that the altered T-cell function because of the PTPN22(1858C>T) 
      polymorphism is exclusively associated with GADA-positive T1D at diagnosis.
FAU - Maziarz, M
AU  - Maziarz M
AD  - Department of Biostatistics, University of Washington, Seattle, WA 98195-7232, 
      USA. marlenam@u.washington.edu
FAU - Janer, M
AU  - Janer M
FAU - Roach, J C
AU  - Roach JC
FAU - Hagopian, W
AU  - Hagopian W
FAU - Palmer, J P
AU  - Palmer JP
FAU - Deutsch, K
AU  - Deutsch K
FAU - Sanjeevi, C B
AU  - Sanjeevi CB
FAU - Kockum, I
AU  - Kockum I
FAU - Breslow, N
AU  - Breslow N
FAU - Lernmark, A
AU  - Lernmark A
CN  - Swedish Childhood Diabetes Register
CN  - Diabetes Incidence in Sweden Study Group
LA  - eng
GR  - DK53004/DK/NIDDK NIH HHS/United States
GR  - R01 DK026190/DK/NIDDK NIH HHS/United States
GR  - P01 DK053004/DK/NIDDK NIH HHS/United States
GR  - DK26910/DK/NIDDK NIH HHS/United States
GR  - 5 P30 DK17047/DK/NIDDK NIH HHS/United States
GR  - P01 DK053004-04/DK/NIDDK NIH HHS/United States
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
GR  - DK053004/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100506
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Autoantibodies)
RN  - 0 (HLA Antigens)
RN  - EC 3.1.3.48 (PTPN22 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 22)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 2)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Autoantibodies/immunology/*metabolism
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Glutamate Decarboxylase/*immunology
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Odds Ratio
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 22/*genetics
MH  - Risk Assessment
MH  - Sweden
PMC - PMC3045194
MID - NIHMS268562
EDAT- 2010/05/07 06:00
MHDA- 2010/10/29 06:00
PMCR- 2011/02/25
CRDT- 2010/05/07 06:00
PHST- 2010/05/07 06:00 [entrez]
PHST- 2010/05/07 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
PHST- 2011/02/25 00:00 [pmc-release]
AID - gene201012 [pii]
AID - 10.1038/gene.2010.12 [doi]
PST - ppublish
SO  - Genes Immun. 2010 Jul;11(5):406-15. doi: 10.1038/gene.2010.12. Epub 2010 May 6.