title: 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.
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.
authors.affiliation: Department of Pediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Susan
authors.initials: S
authors.lastname: Ring
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Diane L
authors.initials: DL
authors.lastname: Wingate
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Pembrey
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001722:Birth Order; D001824:Body Constitution / Q000235:genetics*; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000502:physiology; D005333:Fetus / Q000502:physiology*; D005838:Genotype; D006257:Head / Q000033:anatomy & histology; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D018598:Minisatellite Repeats / Q000235:genetics; D010298:Parity; D011247:Pregnancy / Q000502:physiology*; D015430:Weight Gain / Q000235:genetics*
chemical_list: D007335:Insulin-Like Growth Factor II