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Diabetes Care. 2017 Sep;40(9):1194-1202. doi: 10.2337/dc17-0238. Epub 2017 Jun 23.

Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study.

Author information

1
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL jeffrey.krischer@epi.usf.edu.
2
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
3
Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
4
Pacific Northwest Diabetes Research Institute, Seattle, WA.
5
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO.
6
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA.
7
Department of Pediatrics, Turku University Hospital, Turku, Finland.
8
Department of Physiology, University of Turku, Turku, Finland.
9
Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany.
10
Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
11
Forschergruppe Diabetes e.V., Neuherberg, Germany.
12
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.

Abstract

OBJECTIVE:

We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes.

RESEARCH DESIGN AND METHODS:

Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years.

RESULTS:

Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children). The presence of SNPs rs2476601 (PTPN22) and rs2292239 (ERBB3) demonstrated increased risk of both autoantibodies to insulin (IAA) only and GADA only. SNP rs689 (INS) was protective of IAA only, but not of GADA only. The rs3757247 (BACH2) SNP demonstrated increased risk of GADA only. Male sex, father or sibling as the diabetic proband, introduction of probiotics under 28 days of age, and weight at age 12 months were associated with IAA only, but only father as the diabetic proband and weight at age 12 months were associated with GADA only. Mother as the diabetic proband was not a significant risk factor.

CONCLUSIONS:

These results show clear differences in the initiation of autoimmunity according to genetic factors and environmental exposures that give rise to IAA or GADA as the first appearing indication of autoimmunity.

PMID:
28646072
PMCID:
PMC5566280
DOI:
10.2337/dc17-0238
[Indexed for MEDLINE]
Free PMC Article

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