Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Circulating IGF1 and IGF2 and SNP genotypes in pregnant and non-pregnant women and men. (#170)

Kathy L Gatford 1 , Gary K Heinemann 1 , Steven D Thompson 1 , Jamie V Zhang 1 , Julielie A Owens 1 , Gustaaf A Dekker 1 , Claire T Roberts 1
  1. Robinson Research Institute and School of Paediatrics & Reproductive Health, University of Adelaide, Adelaide, SA, Australia

Circulating IGFs are important regulators of postnatal growth and metabolism and of maternal adaptations, fetal and placental growth and function in pregnancy1. In adults, circulating IGF1 is slightly higher in men than women and IGF2 is similar between sexes, whilst circulating IGF1 but not IGF2 decreases with increasing age. Variable effects of pregnancy on circulating IGFs have been reported, particularly before the third trimester. Single nucleotide polymorphisms (SNPs) in IGF genes or genes that regulate methylation of the IGF2-H19 gene locus also associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children2-5 , but whether this occurs in pregnancy is unknown. We therefore investigated associations of circulating IGF1 and IGF2 with age and genotype at these candidate SNPs in men (n=134), non-pregnant women (n=74), and women at 15 weeks’ gestation (n=98). Circulating IGF1 decreased (P < 0.001) with age, and IGF1 and IGF2 were lower in pregnant than non-pregnant women or men (each P < 0.001). SNP genotypes in the IGF2-H19 locus were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204; overall regression P < 0.001). In single SNP models, associations with IGF2 rs680 were similar in all groups, with higher plasma IGF1 in individuals with the GG than GA (P = 0.016) or grouped GA+AA genotypes (P = 0.003). SNP genotypes in the IGF2-H19 locus were also associated with plasma IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727; overall regression P = 0.001). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium, so these associations could reflect other genotype variation and/or methylation changes within this region. Associations between genotypes in the IGF2-H19 locus and circulating IGF1 and IGF2 concentrations require confirmation in additional independent populations, and do not appear to be affected by pregnancy, which decreases circulating IGFs.

  1. 1. Sferruzzi-Perri AN, Owens JA, Pringle KG & Roberts CT (2011) J Physiol 589:7-20
  2. 2. Vella A, Bouatia-Naji N, Heude B, Cooper J, Lowe C, Petry C, Ring S, Dunger D, Todd J & Ong K (2008) Diabetologia 51:811-815
  3. 3. Albani D, Batelli S, Polito L, Vittori A, Pesaresi M, Gajo G, De Angeli S, Zanardo A, Gallucci M & Forloni G (2009) BMC Geriatrics 9:19
  4. 4. O'Dell SD, Miller GJ, Cooper JA, Hindmarsh PC, Pringle PJ, Ford H, Humphries SE & Day INM (1997). Int J Obes Rel Metab Dis 21:822-825
  5. Petry C, Ong K, Barratt B, Wingate D, Cordell H, Ring S, Pembrey M, Team TAS, Reik W, Todd J, & Dunger D (2005) BMC Genetics 6:22