Geelhoed J J Miranda, Mook-Kanamori Dennis O, Witteman Jacqueline C M, Hofman Albert, van Duijn Cornelia M, Moll Henriëtte A, Steegers Eric A P, Hokken-Koelega Anita C S, Jaddoe Vincent W V
The Generation R Study Group, Department of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 2008 Mar;68(3):382-9. doi: 10.1111/j.1365-2265.2007.03050.x. Epub 2007 Sep 19.
The objective of this study was to examine whether variants of the IGF1 gene are associated with growth patterns from foetal life until infancy.
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.
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).
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.
本研究的目的是检验胰岛素样生长因子1(IGF1)基因的变异是否与从胎儿期到婴儿期的生长模式相关。
本研究纳入了代际R研究,这是一项基于人群的胎儿期前瞻性队列研究。通过超声在孕早期、中期和晚期评估胎儿生长情况(头围、腹围、股骨长度、估计胎儿体重)。在出生时(体重)以及6周、6个月和14个月龄时(头围、身长、体重)评估婴儿期生长情况。对738名儿童的IGF1启动子区域基因型进行了测定。
鉴定出IGF1启动子区域的8个等位基因。总体而言,43%的受试者为最常见的192碱基对等位基因(野生型)纯合子,45%为杂合子,12%为192碱基对等位基因的非携带者。三组之间出生体重无差异。然而,与192碱基对纯合子相比,非携带者在孕中期的估计胎儿体重较低(P = 0.040),随后到6个月时生长速率增加(P < 0.005)。身长方面也发现了类似的生长速率差异(P < 0.001)。
IGF1启动子区域的变异与出生体重无关。然而,192碱基对等位基因的非携带者往往胎儿体型较小,随后从孕中期到婴儿早期生长速率增加。需要在更大的队列中进行研究以重复我们的发现,并检验这些影响是否在整个儿童期持续存在。