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Diabetes-associated HLA genotypes affect birthweight in the general population.

Larsson, Helena LU ; Lynch, Kristian LU ; Lernmark, Barbro LU ; Nilsson, A; Hansson, Gertie LU ; Almgren, Peter LU ; Lernmark, A and Ivarsson, Sten LU (2005) In Diabetologia 48(Jul 1). p.1484-1491
Abstract
Aims/hypothesisThe aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The... (More)
Aims/hypothesisThe aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]=0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/Interpreation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IA-2 autoantibodies, HLA-DQ8, HLA, GAD65 autoantibodies, birthweight, diabetes mellitus, insulin-dependent diabetes, screening, type 1 diabetes, HLA-DQ2
in
Diabetologia
volume
48
issue
Jul 1
pages
1484 - 1491
publisher
Springer Verlag
external identifiers
  • wos:000231219200010
  • pmid:15991024
  • scopus:23844497046
ISSN
1432-0428
DOI
10.1007/s00125-005-1813-4
language
English
LU publication?
yes
id
13def69e-93c0-48e9-a2fe-4c5825f22786 (old id 142411)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15991024&dopt=Abstract
date added to LUP
2007-07-25 09:53:44
date last changed
2017-11-05 03:46:02
@article{13def69e-93c0-48e9-a2fe-4c5825f22786,
  abstract     = {Aims/hypothesisThe aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]=0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/Interpreation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.},
  author       = {Larsson, Helena and Lynch, Kristian and Lernmark, Barbro and Nilsson, A and Hansson, Gertie and Almgren, Peter and Lernmark, A and Ivarsson, Sten},
  issn         = {1432-0428},
  keyword      = {IA-2 autoantibodies,HLA-DQ8,HLA,GAD65 autoantibodies,birthweight,diabetes mellitus,insulin-dependent diabetes,screening,type 1 diabetes,HLA-DQ2},
  language     = {eng},
  number       = {Jul 1},
  pages        = {1484--1491},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Diabetes-associated HLA genotypes affect birthweight in the general population.},
  url          = {http://dx.doi.org/10.1007/s00125-005-1813-4},
  volume       = {48},
  year         = {2005},
}