Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.

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.

Research Design And 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.

Maternally transmitted foetal H19 variants and associations with birth weight.

This study was designed to test the hypothesis that polymorphic variation in maternally transmitted foetal H19 alleles is associated with offspring size at birth and alterations in maternal glucose concentrations in pregnancy. Inferred parent of origins of transmitted alleles from 13 haplotype tag SNPs in the H19 gene region from 845 family (mother, partner, offspring) trios from the prospective Cambridge Baby Growth Study and 315 trios from the retrospective Cambridge Wellbeing Study cohorts were tested for association with offspring size at birth measures, as well as maternal glucose concentrations 1 h after a glucose load at week 28 of pregnancy. The foetal rs2071094 allele inherited from the mother was associated with increased birth weight (p = 0.

Increased placental glucose transport rates in pregnant mice carrying fetuses with targeted disruption of their placental-specific Igf2 transcripts are not associated with raised circulating glucose concentrations.

At the beginning of the third week of pregnancy, mouse fetuses with targeted disruption of their paternally-transmitted insulin-like growth factor 2 gene placental-specific transcripts have growth-restricted placentas but normal body weights due to upregulated placental nutrient transport. We assessed whether increased placental glucose transport rates were associated with raised maternal glucose concentrations by performing intraperitoneal glucose tolerance tests (ipGTT) in pregnant mice carrying knockout pups and comparing them with mice carrying genotype-matched phenotypically wild type pups. Mean ± SD body weights of affected pups were 95 ± 8% of control values at e16 and 73 ± 7% at e18.

Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

Objective: We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Delta13) on maternal glucose concentrations in pregnancy.

Research Design And Methods: Experimental mice were pregnant females that had inherited the disrupted H19(Delta13) from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19(Delta13) through maternal inheritance of the disrupted gene.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth.

Pregnancy insulin, glucose, and BMI contribute to birth outcomes in nondiabetic mothers.

Objective: We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes.

Research Design And Methods: Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records.

Lack of association between common polymorphisms in the 17beta-hydroxysteroid dehydrogenase type V gene (HSD17B5) and precocious pubarche.

Background: 17beta-Hydroxysteroid dehydrogenase (type V; HSD17B5) is a key enzyme involved in testosterone production in females. A single nucleotide polymorphism (SNP) in the promoter region of its gene was recently found to be associated with polycystic ovary syndrome (PCOS) and its related hyperandrogenaemia. Precocious pubarche (PP) is a clinical entity pointing to adrenal androgen excess from mid-childhood onward and is associated with ovarian androgen excess from puberty onward.

Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height.

Objective: The type 2 insulin-like growth factor receptor (IGF2R) is thought to regulate insulin-like growth factor-II (IGF-II) bioavailability by degrading it in the lysosomes after uptake. We hypothesised that polymorphisms in the IGF2R gene could alter size at birth and childhood growth.

Design And Methods: The hypothesis was tested in a normal birth cohort (Avon Longitudinal Study of Parents and Children) by genotyping the IGF2R gene gly1619arg polymorphism, which causes a non-conservative amino acid change in the IGF-II binding region, using PCR and restriction fragment length polymorphism analysis.