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Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age : The teddy study

Krischer, Jeffrey P.; Lynch, Kristian F; Lernmark, Ake LU ; Hagopian, William A; Rewers, Marian J.; She, Jin-Xiong; Toppari, Jorma; Ziegler, Anette G. LU and Akolkar, Beena (2017) In Diabetes Care 40(9). p.1194-1202
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 diabetesrelated 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... (More)

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 diabetesrelated 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 monthswere 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 IAAorGADA as the first appearing indication of autoimmunity.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes , TEDDY study, genetic interactions, enviromental interactions
in
Diabetes Care
volume
40
issue
9
pages
9 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85028082327
  • pmid:28646072
  • wos:000408157800023
ISSN
0149-5992
DOI
10.2337/dc17-0238
language
English
LU publication?
yes
id
be8965ee-2e1b-424d-a5f6-a5002aa8c150
date added to LUP
2017-09-01 15:08:06
date last changed
2018-07-15 04:43:46
@article{be8965ee-2e1b-424d-a5f6-a5002aa8c150,
  abstract     = {<p>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 diabetesrelated 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 monthswere 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 IAAorGADA as the first appearing indication of autoimmunity.</p>},
  author       = {Krischer, Jeffrey P. and Lynch, Kristian F and Lernmark, Ake and Hagopian, William A and Rewers, Marian J. and She, Jin-Xiong and Toppari, Jorma and Ziegler, Anette G. and Akolkar, Beena},
  issn         = {0149-5992},
  keyword      = {Diabetes ,TEDDY study,genetic interactions,enviromental interactions},
  language     = {eng},
  month        = {09},
  number       = {9},
  pages        = {1194--1202},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age : The teddy study},
  url          = {http://dx.doi.org/10.2337/dc17-0238},
  volume       = {40},
  year         = {2017},
}