Context: Intrauterine and postnatal growth influences future risks for metabolic syndrome. Body size and blood pressure (BP) are polygenic traits. The role for genetic variations in growth hormone (GH)-insulin-like growth factor (IGF) axis genes on intrauterine and early childhood growth and blood pressure, as well as gene loci identified through Genome Wide Association Studies (GWAS), are unclear. Objective: To determine whether common variations in the genes of the GH-IGF axis associate with antenatal growth and birth size and play a role in the determination of body size and blood pressure at 3 years of age. Study design: Pregnant women from white European families were recruited by the University College London Fetal Growth Study (n = 774). Fetal growth was measured by ultrasonography at each trimester. Postnatal growth data were collected prospectively at 6 months, 1 year, 2 years and 3 years of age. BP was measured at 3 years of age. Genotyping was performed by a combination of restriction fragment length polymorphism analysis, KBioscience Competitive Allele specific PCR genotyping System (KASP) analysis and multiplex polymerase chain reaction (PCR). Results: The GHR exon 3 deletion genotype was significantly associated with birth weight and placental weight. IGF1 SNPs did not demonstrate significant consistent longitudinal association with parameters investigated. IGF2 SNPs were significantly associated with intrauterine growth (rs680), birth weight (rs680), placental weight (rs680) and BP (rs3842759) at 3 years of age. Several SNPs in genes found to be associated with adult BMI and BP from GWAS were significantly associated with early childhood size (MTCH2, SH2B3), body composition (SH2B1, TMEM18) and BP (FTO). Conclusion: These data suggest that several polymorphisms in the GH-IGF axis and in GWAS-identified genes for adult BMI and BP are significantly associated with intrauterine and early childhood size and BP at 3 years of age.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626206 |
| Date | January 2013 |
| Creators | Padidela, R. N. R. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1396005/ |
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