Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain

Ken K Ong, Clive J Petry, Bryan J Barratt, Susan Ring, Heather J Cordell, Diane L Wingate, Marcus E Pembrey, John A Todd, David B Dunger, ALSPAC Study Team

Research output: Contribution to journalArticle (Academic Journal)peer-review

54 Citations (Scopus)

Abstract

Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size. Therefore, this variant is a potential contributory factor to the reported fetal origins of adult disease. In the population-based Avon Longitudinal Study of Pregnancy and Childhood birth cohort, we have confirmed in the present study the association between the INS VNTR III/III genotype and larger head circumference at birth (odds ratio [OR] 1.92, 95% CI 1.23-3.07; P = 0.004) and identified an association with higher cord blood IGF-II levels (P = 0.05 to 0.0001). The genotype association with head circumference was influenced by maternal parity (birth order): the III/III OR for larger head circumference was stronger in second and subsequent pregnancies (OR 5.0, 95% CI 2.2-11.5; P = 0.00003) than in first pregnancies (1.2, 0.6-2.2; P = 0.8; interaction with birth order, P = 0.02). During childhood, the III/III genotype remained associated with larger head circumference (P = 0.004) and was also associated with greater BMI (P = 0.03), waist circumference (P = 0.03), and higher fasting insulin levels in girls (P = 0.02). In addition, there were interactions between INS VNTR genotype and early postnatal weight gain in determining childhood BMI (P = 0.001 for interaction), weight (P = 0.005), and waist circumference (P = 0.0005), such that in the approximately 25% of children (n = 286) with rapid early postnatal weight gain, class III genotype-negative children among this group gained weight more rapidly. Our results indicate that complex prenatal and postnatal gene-maternal/fetal interactions influence size at birth and childhood risk factors for adult disease.

Original languageEnglish
Pages (from-to)1128-33
Number of pages6
JournalDiabetes
Volume53
Issue number4
Publication statusPublished - Apr 2004

Keywords

  • Birth Order
  • Body Constitution
  • Body Mass Index
  • Cohort Studies
  • Female
  • Fetal Blood
  • Fetus
  • Genotype
  • Head
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor II
  • Minisatellite Repeats
  • Parity
  • Pregnancy
  • Weight Gain

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