Di-Nucleotide Repeat Polymorphisms of the Insulin-Like Growth Factor-1 Gene and Their Association with IGF-1, Insulin-Like Growth Factor-Binding Protein-1 and Birth Size in a Sri-Lankan Cohort

Abstract

Background: Insulin-like growth factor (IGF)-I is implicated in fetal growth. Ethnic variations of IGF-1 have also been suggested. Di-nucleotide repeat polymorphisms of the IGF-1 gene or their association with IGF-1 levels and birth size have not been studied in Sri Lankans. Objectives: To describe IGF-1 di-nucleotide repeat polymorphisms and their association with IGF-1 and IGF-binding protein (IGFBP)-1 levels and birth size in a cohort of Sri Lankans. Methods: A cross-sectional study on 200 mother-newborn pairs was carried out. Maternal and cord blood levels of IGF-1 and IGFBP-1 were measured by enzyme-linked immunosorbent assay. Three di-nucleotide repeat polymorphisms of the IGF-1 gene [cytosine-adenine (CA) repeats in the promoter and 3′ regions and intron 2 cytosine-thymine (CT) repeat] were studied using PCR amplification and fragment analysis. Results:Cord blood IGFBP-1 levels correlated negatively with birth weight (p < 0.01) and crown-heel length (p < 0.05). Wild-type alleles of the CA repeat polymorphisms differed from those reported in other populations. Newborn and maternal intron 2 CT repeat polymorphism showed a significant effect on birth weight (p < 0.01 and p < 0.001, respectively), crown-heel length (p < 0.01) and head circumference (p < 0.01 and p < 0.05, respectively). Promoter region CA repeat polymorphism and intron 2 CT repeat polymorphism in the newborns were significantly (p < 0.05) associated with cord blood IGF-1 levels. Almost all these effects were limited to primiparous pregnancies. Conclusions: In Sri Lankans intron 2 CT repeat polymorphism of the IGF-1 gene appears to be a significant contributor to IGF-1 levels and birth size in primiparous pregnancies.

Association of Cord Blood Leptin, Soluble Leptin Receptor, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-1 on Birth Indices in Healthy Full-Term Newborns

“…Several studies have shown cord blood IGF-I also to be gender-specific with higher levels reported in females [3,19,20]. However, we did not observe a gender effect on cord blood IGF-I levels in our previous study [13]. Similarly, there are other studies in which male and female newborns were found to have comparable levels of cord blood IGF-I [21].…”

“…110 healthy appropriately grown term (delivered 37 + 0 to 39 + 6 completed weeks) newborns born following a singleton uncomplicated pregnancy in healthy women were selected from a previous study [13], based on the availability of aliquots of cord plasma for determination of leptin and SLR levels. Samples were collected over a 2-year period between January 2007 and December 2008.…”

“…Samples were collected over a 2-year period between January 2007 and December 2008. Clinical characteristics of the main group as well as IGF-I and IGFBP-1 levels have been described previously [13]. The study was approved by the institutional review board and mothers gave written informed consent.…”

“…The intra- and interassay coefficient of variance for both assays were <8%. IGF-I and IGFBP-1 levels had been previously measured using enzyme immunoassay (IGF-I; EIA-2947: DRG International, Inc., USA, and IGFBP-1 (REF-10851): Medix Biochemica, Kauniainer, Finland) and details reported elsewhere [13]. Birth weight was measured immediately after delivery and crown-heel length and head circumference were measured within 24 h after delivery [13].…”

“…Several investigators have shown that birth weight is correlated positively with IGF-I, and negatively with IGFBP-1 [10,11,12]. In our recent studies on full-term newborns, an effect of IGF-I on birth indices was not seen, but IGFBP-1 exerted a significant negative effect [13]. …”