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


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.
Winkler
Christiane
C
Institut fuer Diabetesforschung der Forschergruppe Diabetes e.V. at the Helmholtz Center Munich, 85764 Neuherberg, Germany.
Illig
Thomas
T
Koczwara
Kerstin
K
Bonifacio
Ezio
E
Ziegler
Anette-Gabriele
AG
D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006442:Glycated Hemoglobin / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007339:Insulysin / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D011446:Prospective Studies; D014157:Transcription Factors / Q000235:genetics*; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases
D027682:Cation Transport Proteins; D051360:Cyclin-Dependent Kinase 5; D006442:Glycated Hemoglobin; D018398:Homeodomain Proteins; D007339:Insulysin; D014157:Transcription Factors; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases; C078492:HHEX protein, human; C492522:SLC30A8 protein, human; C517652:hemoglobin A1c protein, human; C525110:CDKAL1 protein, human