Association of macrophage migration-inhibitory factor gene and growth differentiation factor 15 gene polymorphisms and their circulating levels with respiratory distress syndrome among preterm neonates.

Abstract

Background: In preterm newborns, neonatal respiratory distress syndrome (RDS) is among the main causes of respiratory failure and mortality. However, the effect of macrophage migration-inhibitory factor (MIF) on neonatal developmental lung disease is not well documented in the literature. Moreover, little is known about the effects of growth differentiation factor-15 (GDF-15) on lung maturity in preterm infants.

Purpose: To evaluate serum MIF and GDF-15 levels in preterm infants with and without RDS and analyze the genetic profile of single nucleotide polymorphisms (SNPs) for MIF rs755622 G>C and GDF-15 rs4808793 C>G.

Methods: In this case-control study, 90 preterm newborns were categorized into 3 groups: group A included 30 preterm newborns with mild to moderate RDS, group B included 30 preterm newborns with severe RDS, and group C included 30 healthy preterm newborns. Enzyme-linked immunosorbent assay methods were used to measure serum MIF and GDF-15 levels. The MIF rs755622 G>C and GDF-15 rs4808793 C>G SNPs were analyzed by restriction fragment length polymorphism-polymerase chain reaction.

Results: Significantly higher median MIF and GDF-15 blood levels were noted among neonates with severe RDS (17.32 μg/L and 3.19 pg/mL, respectively) versus those with mild to moderate RDS (5.50 μg/L and 0.71 pg/mL, respectively) (P<0.05 for both). A significantly higher frequency of a mutant C-allele of MIF rs755622 G>C was noted among cases (37.5%) versus controls (13.3%) (P=0.001; odds ratio [OR], 0.256; 95% confidence interval [CI], 0.112-0.589). A significantly higher frequency of a mutant G-allele of GDF-15 rs4808793 C>G SNPs was noted among cases (49.2%) versus controls (30%) (OR, 0.443; 95% CI, 0.229-0.856).

Conclusion: These findings suggest that serum MIF and GDF-15 levels are strongly associated with RDS severity among preterm neonates. Moreover, polymorphisms of MIF and GDF-15 could be genetic risk factors for the development of neonatal RDS among preterm babies.