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A population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 is associated with high birthweight in Finnish diabetic families

Genes & Immunity volume 9, pages 207–213 (2008)Cite this article

Abstract

Children with type 1 diabetes (T1D) susceptibility HLA genotypes are shown to have an increased birthweight. We investigated to what extent T1D-predisposing HLA haplotypes were associated with increased birthweight. A total of 1255 Finnish children comprising those with T1D and their non-diabetic siblings were investigated. A total of 342 children and their non-diabetic parents were HLA genotyped. Birthweight data were obtained from the national Medical Birth Registry. The population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 was associated with high birthweight (P=0.0280) in families with a diabetic offspring. Other T1D-predisposing HLA haplotypes showed nonsignificant tendency with high birthweight. More infants with a birthweight ⩾4000 g were born in families with a T1D offspring than in the general Finnish population (P=0.0139). The previously observed direct association between birthweight and T1D risk may be mediated through the modulating effects that T1D susceptibility HLA genes have on weight. High birthweight and subsequent weight gain may accelerate the ongoing pancreatic autoimmune process in genetically susceptible individuals. The high proportion of infants having a birthweight ⩾4000 g in families with a diabetic offspring raises a concern of potential adverse health outcomes that high birthweight can have.

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Acknowledgements

We thank Jianjun Wang, Lotta Siira, Liisa Saarikoski, Jari Suutari and Pekka Hyvärinen for their excellent help during the study. The study was supported by the Sigrid Jusélius Foundation.

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Authors and Affiliations

  1. Department of Health Promotion and Chronic Disease Prevention, Diabetes Unit, National Public Health Institute, Helsinki, Finland

    T M Järvinen, V Harjutsalo, L Kinnunen, E Tuomilehto-Wolf & J Tuomilehto

  2. Department of Public Health, University of Helsinki, Helsinki, Finland

    L Kinnunen, M E Miettinen & J Tuomilehto

  3. South Ostrobothnia Central Hospital, Seinäjoki, Finland

    J Tuomilehto

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  1. T M Järvinen
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Correspondence to T M Järvinen.

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Järvinen, T., Harjutsalo, V., Kinnunen, L. et al. A population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 is associated with high birthweight in Finnish diabetic families. Genes Immun 9, 207–213 (2008). https://doi.org/10.1038/gene.2008.3

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