HHEX-IDE polymorphism is associated with low birth weight in offspring with a family history of type 1 diabetes

J Clin Endocrinol Metab. 2009 Oct;94(10):4113-5. doi: 10.1210/jc.2009-0970. Epub 2009 Jul 21.


Context: The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion also reduce birth weight, and an association of low birth weight and the type 2 diabetes risk alleles at the HHEX-IDE and CDKAL1 loci were recently reported.

Objective: Here, we examined the relationship between type 2 diabetes risk alleles and birth weight in a diabetic environment presented in children of mothers with type 1 diabetes.

Research design and methods: Birth weight and genotyping of single nucleotide polymorphisms (SNPs) at the CDKAL1, HHEX-IDE, and SLC30A8 loci was obtained and analyzed in 729 singleton full-term children of mothers with type 1 diabetes born in Germany.

Results: The fetal risk alleles of HHEX-IDE SNP rs5015480 and SNP rs10882102 were associated with reduced birth weight: 81g (95% confidence interval, 20-140 g; P = 0.009) and 85 g (95% confidence interval, 25-145 g; P = 0.005) lower birth weight per risk allele, respectively. The association remained significant after adjusting for maternal pregnancy-glycosylated hemoglobin. Fetal genotypes at the CDKAL1 and SLC30A8 loci were not associated with birth weight in this cohort.

Conclusions: The association of low birth weight and type 2 diabetes risk alleles of the HHEX-IDE locus is confirmed in children of mothers with type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cation Transport Proteins / genetics
  • Cyclin-Dependent Kinase 5 / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Germany
  • Glycated Hemoglobin A / metabolism
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant, Low Birth Weight*
  • Infant, Newborn
  • Insulysin / genetics*
  • Male
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Pregnancy Trimester, Third / blood
  • Prospective Studies
  • Transcription Factors / genetics*
  • Zinc Transporter 8
  • tRNA Methyltransferases


  • Cation Transport Proteins
  • Glycated Hemoglobin A
  • HHEX protein, human
  • Homeodomain Proteins
  • SLC30A8 protein, human
  • Transcription Factors
  • Zinc Transporter 8
  • hemoglobin A1c protein, human
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human
  • Insulysin