TY - JOUR
T1 - HHEX-IDE polymorphism is associated with low birth weight in offspring with a family history of type 1 diabetes
AU - Winkler, Christiane
AU - Illig, Thomas
AU - Koczwara, Kerstin
AU - Bonifacio, Ezio
AU - Ziegler, Anette Gabriele
N1 - Funding Information:
This work was supported by grants from the Juvenile Diabetes Research Foundation (JDRF no. 1-2006-665), the German Research Foundation (Deutsche Forschungsgemeinschaft ZI 310/14-1 and 14-2), the German National Genome Research Network, and the Helmholtz Center Munich, German Research Center for Environmental Health. This work was also supported by the Kompetenznetz Diabetes mellitus (Competence Network for Diabetes mellitus), funded by the Federal Ministry of Education and Research (FKZ 01GI0805-07).
PY - 2009
Y1 - 2009
N2 - 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 85g (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.
AB - 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 85g (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.
UR - http://www.scopus.com/inward/record.url?scp=70349925566&partnerID=8YFLogxK
U2 - 10.1210/jc.2009-0970
DO - 10.1210/jc.2009-0970
M3 - Article
C2 - 19622614
AN - SCOPUS:70349925566
SN - 0021-972X
VL - 94
SP - 4113
EP - 4115
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -
