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Genetics

BMI at Age 8 Years Is Influenced by the Type 2 Diabetes Susceptibility Genes HHEX-IDE and CDKAL1

  1. Christiane Winkler1,
  2. Ezio Bonifacio2,
  3. Harald Grallert3,
  4. Lydia Henneberger1,
  5. Thomas Illig3 and
  6. Anette-Gabriele Ziegler MD1,4
  1. 1Institut fuer Diabetes forschung der Forschergruppe Diabetes e.V. at Helmholtz Center Munich, Neuherberg, Germany;
  2. 2Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany;
  3. 3Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany;
  4. 4Forschergruppe Diabetes der Technischen Universitaet Muenchen, Munich, Germany.
  1. Corresponding author: Anette-Gabriele Ziegler, anziegler{at}lrz.uni-muenchen.de.
Diabetes 2010 Aug; 59(8): 2063-2067. https://doi.org/10.2337/db10-0099
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Abstract

OBJECTIVE To determine whether HHEX-IDE and CDKAL1 genes, which are associated with birth weight and susceptibility to type 2 diabetes, continue to influence growth during childhood.

RESEARCH DESIGN AND METHODS BMI, weight, and height at age 8 years expressed as age- and sex-corrected standard deviation scores (SDS) against national reference data and single-nucleotide polymorphism genotyping of HHEX-IDE and CDKAL1 loci were analyzed in 646 prospectively followed children in the German BABYDIAB cohort. All children were singleton full-term births; 386 had mothers with type 1 diabetes, and 260 had fathers with type 1 diabetes and a nondiabetic mother.

RESULTS Type 2 diabetes risk alleles at the HHEX-IDE locus were associated with reduced BMI-SDS at age 8 years (0.17 SDS per allele; P = 0.004). After stratification for birth weight, both HHEX-IDE and CDKAL1 risk alleles were associated with reduced BMI-SDS (0.45 SDS, P = 0.0002; 0.52 SDS, P = 0.0001) and weight-SDS (0.22 SDS, P = 0.04; 0.56 SDS, P = 0.0002) in children born large for gestational age (>90th percentile) but not children born small or appropriate for gestational age. Within children born large for gestational age, BMI and weight decreased with each additional type 2 diabetes risk allele (∼ −2 kg per allele; >8 kg overall). Findings were consistent in children of mothers with type 1 diabetes (P < 0.0001) and children of nondiabetic mothers (P = 0.008).

CONCLUSIONS The type 2 diabetes susceptibility alleles at HHEX-IDE and CDKAL1 loci are associated with low BMI at age 8 years in children who were born large for gestational age.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • © 2010 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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BMI at Age 8 Years Is Influenced by the Type 2 Diabetes Susceptibility Genes HHEX-IDE and CDKAL1
Christiane Winkler, Ezio Bonifacio, Harald Grallert, Lydia Henneberger, Thomas Illig, Anette-Gabriele Ziegler
Diabetes Aug 2010, 59 (8) 2063-2067; DOI: 10.2337/db10-0099

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BMI at Age 8 Years Is Influenced by the Type 2 Diabetes Susceptibility Genes HHEX-IDE and CDKAL1
Christiane Winkler, Ezio Bonifacio, Harald Grallert, Lydia Henneberger, Thomas Illig, Anette-Gabriele Ziegler
Diabetes Aug 2010, 59 (8) 2063-2067; DOI: 10.2337/db10-0099
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