Lack of association between insulin-like growth factor 1 receptor G+3174A polymorphism and retinopathy of prematurity

Background: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that affects premature infants. Insulin-like growth factor I (IGF-I) has been established as being necessary for vascular growth in the neonatal retina. Low IGF-I levels during the early postnatal days have been found to be predictive for ROP. The effects of IGF-I are mediated through IGF-I receptors (IGF-IR), which, in turn, suppress IGF-I production. The G(+3174)A polymorphism of the IGF-IR gene has been shown to be associated with low IGF-I levels. We tested the association of this IGF-IR polymorphism with ROP. Methods: We enrolled in the ROP group those infants (n=108) who had been treated with laser or cryo therapy due to ROP stage 2+ or 3 (n=91) or had a ROP stage 4 or 5 (n=17) (ROP group). The median gestational age of these infants was 28 weeks (range 24-35 weeks) and birth weight was 970 g (range 630 to 2,000 g). The distribution of IGFR-1 G(>+3174)A genotype in the ROP group was compared to that in 120 gestational age-matched infants with ROP stage 1 or 2 not requiring intervention [gestational age 30 (range 24-37) weeks, birth weight 1,235 (640-1,960) g] (LBW group) and 164 term newborns [gestational age 39 (range 35-42) weeks, birth weight 3,450 (2,500-4,350) g] (term group). Genotyping was done using PCR-RFLP methods. Result: The prevalence of IGF-IR G(+3174)A polymorphism was the same in the ROP group, the LBW group and the term group, showing no association between this single-nucleotide polymorphism (SNP) and ROP. Conclusion: Our results do not support the hypothesis that the carrier state of IGF-IR G(+3174)A polymorphism has an impact on the risk of ROP in infants. A possible cause for the lack of association is that the rapid nutritional and metabolic changes during postnatal life have a greater effect on IGF-I levels than this SNP does.