Published online February 1, 2006
PEDIATRICS
Vol. 117
No. 2
February 2006, pp.
591-592
(doi:10.1542/peds.2005-2809)
A Prevalent Functional Polymorphism of Insulin-Like Growth Factor System Is Not Associated With Perinatal Complications in Preterm Infants
Ádám Balogh
András Treszl
First Department of Pediatrics,
Semmelweis University,
H-1083 Budapest, Hungary
Ádám Vannay
Barna Vásárhelyi
Research Laboratory of Pediatrics and Nephrology,
Hungarian Academy of Sciences,
H-1083 Budapest, Hungary
To the Editor.—
Two years ago in Pediatrics, Hellstrom et al1 reported the results of their extensive work about the importance of insulin-like growth factors (IGFs) in perinatal pathology. They demonstrated that low serum IGF levels in preterm infants are associated with the risk of intraventricular hemorrhage, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity. Others also found that IGF may also be relevant in the pathogenesis of respiratory distress and BPD in preterm infants.2 These findings suggest that, in addition to its impact on intrauterine and postnatal development,3,4 a low serum IGF level may be of importance in postnatal complications.5
In addition to a number of factors, IGF levels are determined by single-nucleotide polymorphisms (SNPs). The most prevalent SNP is located on IGF-I receptor (IGF-IR) gene at site +3174 with a transition of guanine to adenine. A study showed that carriers of A allele exhibit low levels of free plasma IGF-I.6
Based on the assumed importance of IGF-I in perinatal morbidity, we tested whether carriers of IGF-IR +3174A alleles are at increased risk for any of the prevalent perinatal complications in low birth weight (LBW) preterm infants. Therefore, in our retrospective study, we genotyped dried blood specimens of 132 LBW infants and related the carrier state of IGF-IR alleles to complications (for details, see Table 1).
We found no association between the IGF-IR G+3174A genotype and any of the analyzed perinatal complications. This finding does not support our original hypothesis that infants with an inherited susceptibility for low serum IGF-I levels (ie, carriers of IGF-IR A+3174 alleles) are at increased risk for perinatal morbidity. An explanation for the lack of association may be that the impact on IGF-I levels of the rapid metabolic and nutritional changes that premature infants experience is greater than the impact of SNPs. Infants who are born prematurely suddenly lose their main intrauterine source of IGF-I, namely amniotic fluid. Also, postnatal IGF-I levels are strongly influenced by nutrition, severe infection, acidosis, and other metabolic disturbances.7 These conditions are prevalent in preterm populations and their impact on postnatal IGF-I levels could be greater than the impact of genotypes. However, the lack of a statistically significant association between IGF-IR G+3174A SNP and risk of perinatal complications does not exclude the possibility that the carrier state of this SNP could be important in some patients. This would suggest the need for additional studies comparing IGF-I levels with the IGF-IR genotypes.
ACKNOWLEDGMENTS
This study was supported by National Scientific Research Foundation grant OTKA T046086 and National Developmental Found grant NKFP 1A/002/2004.
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