title: Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.
abstract: OBJECTIVE
  To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy.
  
  
  METHODS
  A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Baby Growth Study (n = 845 trios) and the retrospective Cambridge Wellbeing Study (n = 315 trios) (3,480 samples in total). Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights.
  
  
  RESULTS
  Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03). In contrast, there were no associations between maternal glucose concentrations and maternal or maternally transmitted fetal IGF2 genotypes.
  
  
  CONCLUSIONS
  Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother. The association may be at least partially mediated by changes in placental IGF2 expression.
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK. cjp1002@cam.ac.uk
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Rachel V
authors.initials: RV
authors.lastname: Seear
authors.forename: Dianne L
authors.initials: DL
authors.lastname: Wingate
authors.forename: Lucy
authors.initials: L
authors.lastname: Manico
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Acerini
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Ieuan A
authors.initials: IA
authors.lastname: Hughes
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000209:etiology*; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000209:etiology*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D012189:Retrospective Studies; D012747:Sexual Partners; D006113:United Kingdom
chemical_list: D001786:Blood Glucose; C035170:IGF2 protein, human; D011257:Pregnancy Proteins; D007335:Insulin-Like Growth Factor II; D005947:Glucose