PMID- 28520980
OWN - NLM
STAT- MEDLINE
DCOM- 20170920
LR  - 20221207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 102
IP  - 8
DP  - 2017 Aug 1
TI  - Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet 
      Relatives at Risk for Type 1 Diabetes?
PG  - 2873-2880
LID - 10.1210/jc.2016-4003 [doi]
AB  - CONTEXT: Genome-wide association studies identified >50 type 1 diabetes (T1D) 
      associated non-human leukocyte antigens (non-HLA) loci. OBJECTIVE: The purpose of 
      this study was to assess the contribution of non-HLA single nucleotide 
      polymorphisms (SNPs) to risk of disease progression. DESIGN AND SETTING: The 
      TrialNet Pathway to Prevention Study follows relatives of T1D patients for 
      development of autoantibodies (Abs) and T1D. PARTICIPANTS: Using the Immunochip, 
      we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk 
      non-Hispanic white relatives. MAIN OUTCOME MEASURE: Effect of SNPs on the 
      development of multiple Abs and T1D. RESULTS: Cox proportional analyses included 
      all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at 
      initial screening, initial Ab type, and number. Factors involved in progression 
      from single to multiple Abs included age at screening, relationship to proband, 
      HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant 
      factors for diabetes progression included age at screening, Ab number, HLA 
      genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B 
      adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, 
      factors involved in disease progression included glucose AUC, age at screening, 
      Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and 
      rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, 
      sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were 
      significantly associated with progression to diabetes in participants <12 years 
      old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) 
      were significant in those >/=12. CONCLUSIONS: In conclusion, we identified five 
      non-HLA SNPs associated with increased risk of progression from Ab positivity to 
      disease that may improve risk stratification for prevention trials.
CI  - Copyright (c) 2017 by the Endocrine Society
FAU - Steck, Andrea K
AU  - Steck AK
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz 
      Medical Campus, Aurora, Colorado 80045.
FAU - Xu, Ping
AU  - Xu P
AD  - Health Informatics Institute, University of South Florida, Tampa, Florida 33612.
FAU - Geyer, Susan
AU  - Geyer S
AD  - Health Informatics Institute, University of South Florida, Tampa, Florida 33612.
FAU - Redondo, Maria J
AU  - Redondo MJ
AD  - Pediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College 
      of Medicine, Houston, Texas 77030.
FAU - Antinozzi, Peter
AU  - Antinozzi P
AD  - Center for Diabetes Research, Wake Forest School of Medicine, Winston Salem, 
      North Carolina 27157.
FAU - Wentworth, John M
AU  - Wentworth JM
AD  - Division of Population Health and Immunity, The Walter and Eliza Hall Institute 
      of Medical Research, Parkville, Victoria 3052, Australia.
AD  - Royal Melbourne Hospital Department of Medicine, University of Melbourne, 
      Parkville, Victoria 3050, Australia.
FAU - Sosenko, Jay
AU  - Sosenko J
AD  - Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, 
      University of Miami School of Medicine, Miami, Florida 33136.
FAU - Onengut-Gumuscu, Suna
AU  - Onengut-Gumuscu S
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, 
      Virginia 22903.
FAU - Chen, Wei-Min
AU  - Chen WM
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, 
      Virginia 22903.
FAU - Rich, Stephen S
AU  - Rich SS
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, 
      Virginia 22903.
FAU - Pugliese, Alberto
AU  - Pugliese A
AD  - Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, 
      University of Miami School of Medicine, Miami, Florida 33136.
AD  - Diabetes Research Institute and Department of Microbiology and Immunology, 
      University of Miami School of Medicine, Miami, Florida 33136.
CN  - Type 1 Diabetes TrialNet Study Group
LA  - eng
GR  - U01 DK085476/DK/NIDDK NIH HHS/United States
GR  - U01 DK061010/DK/NIDDK NIH HHS/United States
GR  - U01 DK085466/DK/NIDDK NIH HHS/United States
GR  - U01 DK103153/DK/NIDDK NIH HHS/United States
GR  - U01 DK061058/DK/NIDDK NIH HHS/United States
GR  - U01 DK085505/DK/NIDDK NIH HHS/United States
GR  - U01 DK085453/DK/NIDDK NIH HHS/United States
GR  - U01 DK085499/DK/NIDDK NIH HHS/United States
GR  - U01 DK085463/DK/NIDDK NIH HHS/United States
GR  - U01 DK103266/DK/NIDDK NIH HHS/United States
GR  - U01 DK107014/DK/NIDDK NIH HHS/United States
GR  - U01 DK061042/DK/NIDDK NIH HHS/United States
GR  - U01 DK061034/DK/NIDDK NIH HHS/United States
GR  - U01 DK085461/DK/NIDDK NIH HHS/United States
GR  - U01 DK085509/DK/NIDDK NIH HHS/United States
GR  - U01 DK103180/DK/NIDDK NIH HHS/United States
GR  - U01 DK085465/DK/NIDDK NIH HHS/United States
GR  - U01 DK085504/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Autoantibodies)
RN  - 0 (Blood Glucose)
RN  - 0 (CCR7 protein, human)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GLIS3 protein, human)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Insulin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Repressor Proteins)
RN  - 0 (SH2B3 protein, human)
RN  - 0 (SLC30A8 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Transporter 8)
RN  - 0 (islet cell antibody)
RN  - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 8)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Area Under Curve
MH  - Autoantibodies/*immunology
MH  - Blood Glucose/metabolism
MH  - CTLA-4 Antigen/genetics
MH  - Cation Transport Proteins/immunology
MH  - Child
MH  - DNA-Binding Proteins
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Disease Progression
MH  - *Family
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glucose Tolerance Test
MH  - Glutamate Decarboxylase/immunology
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - Insulin/immunology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Proteins/genetics
MH  - RNA, Long Noncoding/genetics
MH  - Receptor-Like Protein Tyrosine Phosphatases, Class 8/immunology
MH  - Receptors, CCR7/genetics
MH  - Repressor Proteins
MH  - Risk
MH  - Risk Assessment
MH  - Trans-Activators
MH  - Transcription Factors/genetics
MH  - White People/genetics
MH  - Young Adult
MH  - Zinc Transporter 8
PMC - PMC5546868
EDAT- 2017/05/19 06:00
MHDA- 2017/09/21 06:00
PMCR- 2018/08/01
CRDT- 2017/05/19 06:00
PHST- 2016/12/21 00:00 [received]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/05/19 06:00 [pubmed]
PHST- 2017/09/21 06:00 [medline]
PHST- 2017/05/19 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 3828543 [pii]
AID - jcem_20164003 [pii]
AID - 10.1210/jc.2016-4003 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2017 Aug 1;102(8):2873-2880. doi: 10.1210/jc.2016-4003.