Variation in the IGF1 gene and growth in foetal life and infancy. The Generation R Study.
Geelhoed JJM., Mook-Kanamori DO., Witteman JCM., Hofman A., van Duijn CM., Moll HA., Steegers EAP., Hokken-Koelega ACS., Jaddoe VWV.
OBJECTIVE: The objective of this study was to examine whether variants of the IGF1 gene are associated with growth patterns from foetal life until infancy. STUDY DESIGN AND MEASUREMENTS: This study was embedded in the Generation R Study, a population-based prospective cohort study of foetal life. Foetal growth (head circumference, abdominal circumference, femur length, estimated foetal weight) was assessed by ultrasound in early, mid- and late pregnancy. Growth in infancy was assessed at birth (weight) and at the ages of 6 weeks, 6 months and 14 months (head circumference, length, weight). The IGF1 promoter region genotype was determined in 738 children. RESULTS: Eight alleles of the IGF1 promoter region were identified. In total, 43% of the subjects were homozygous for the most common 192-bp allele (wild-type), 45% were heterozygous, and 12% were noncarriers of the 192-bp allele. No differences were found in birthweight between the three groups. However, noncarriers had a lower estimated foetal weight in mid-pregnancy (P = 0.040), followed by an increased growth rate until 6 months (P < 0.005) in comparison to the 192-bp homozygotes. A similar difference in growth rate was found for length (P < 0.001). CONCLUSIONS: Variants of the IGF1 promoter region are not associated with birthweight. However, noncarriers of the 192-bp allele tend to have a smaller foetal size, followed by an increased growth rate from mid-pregnancy to early infancy. Studies in larger cohorts are necessary to replicate our findings and to examine whether these effects persist throughout childhood.