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Insulin family polymorphisms in pregnancies complicated by small for gestational age infants

Prabha H Andraweera1, Kathryn L Gatford1, Gustaaf A Dekker2

  • 1School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, Australia.

Molecular Human Reproduction
|June 20, 2015
PubMed

Insights

Genetic variations in the insulin receptor gene (INSR) are linked to babies born small for gestational age (SGA). This INSR polymorphism may also increase risks for vascular and metabolic issues later in life.

Area of Science:

  • Genetics
  • Perinatal Medicine
  • Endocrinology

Background:

  • Small for gestational age (SGA) births are associated with increased risks for adverse perinatal outcomes and later-life metabolic and vascular disorders.
  • The insulin family is crucial for regulating intrauterine growth.
  • Specific genetic variations (SNPs) in insulin pathway genes may influence fetal growth and pregnancy outcomes.

Purpose of the Study:

  • To investigate the association between functional single nucleotide polymorphisms (SNPs) in the insulin (INS), insulin receptor (INSR), and insulin receptor substrate 2 (IRS2) genes and small for gestational age (SGA) pregnancies.
  • To examine the relationship between these SNPs, uterine and umbilical artery Doppler findings, and plasma insulin levels.

Main Methods:

  • A nested case-control study involving 1401 nulliparous Caucasian women, their partners, and infants (216 SGA, 1185 uncomplicated).
  • SGA defined as birthweight below the 10th customized percentile, adjusted for multiple factors.
  • Genotyping of SNPs in parent-infant trios using Sequenom MassARRAY; plasma insulin levels measured in non-pregnant adults.

Main Results:

  • The paternal and infant INSR rs2059806 AA genotype was significantly associated with SGA.
  • The infant INSR rs2059806 A allele was linked to abnormal umbilical artery Doppler findings.
  • Individuals with the INSR rs2059806 AA genotype exhibited lower plasma insulin levels compared to heterozygotes and GG homozygotes.

Conclusions:

  • The INSR rs2059806 SNP, previously associated with adult vascular and metabolic diseases, is also associated with SGA pregnancies.
  • This genetic polymorphism may contribute to the risk of developing vascular and metabolic disorders throughout the lifespan.
  • Findings highlight a potential genetic link between intrauterine growth and long-term health outcomes.

Keywords:
SGASNPinsulin receptorpolymorphismrs2059806

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