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Type: Journal article
Title: Insulin family polymorphisms in pregnancies complicated by small for gestational age infants
Author: Andraweera, P.
Gatford, K.
Dekker, G.
Leemaqz, S.
Russell, D.
Thompson, S.
McCowan, L.
Roberts, C.
Citation: Molecular Human Reproduction, 2015; 21(9):745-752
Publisher: Oxford University Press
Issue Date: 2015
ISSN: 1360-9947
Statement of
Prabha H. Andraweera, Kathryn L. Gatford, Gustaaf A. Dekker, Shalem Leemaqz, Darryl Russell, Steven D. Thompson, Lesley McCowan, and Claire T. Roberts on behalf of the SCOPE consortium
Abstract: Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous individuals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course.
Keywords: insulin receptor; SNP; polymorphism; SGA; rs2059806
Description: First published online: June 18, 2015
Rights: © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
RMID: 0030030706
DOI: 10.1093/molehr/gav031
Grant ID:
Appears in Collections:Obstetrics and Gynaecology publications

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