Association of a FGFR-4 Gene Polymorphism with Bronchopulmonary Dysplasia and Neonatal Respiratory Distress

Abstract

Background. Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of premature birth, characterized by impaired alveolar development and inflammation. Pathomechanisms contributing to BPD are poorly understood. However, it is assumed that genetic factors predispose to BPD and other pulmonary diseases of preterm neonates, such as neonatal respiratory distress syndrome (RDS). For association studies, genes upregulated during alveolarization are major candidates for genetic analysis, for example,matrix metalloproteinases (MMPs)andfibroblast growth factors (FGFs)and their receptors(FGFR).Objective. Determining genetic risk variants in a Caucasian population of premature neonates with BPD and RDS.Methods. We genotyped 27 polymorphisms within 14 candidate genes via restriction fragment length polymorphism (RFLP):MMP-1, -2, -9, and -12, -16, FGF receptors 2 and 4, FGF-2, -3, -4, -7, and -18, Signal-Regulatory Proteinα(SIRPA)andThyroid Transcription Factor-1 (TTF-1).Results. Five single nucleotide polymorphisms (SNPs) inMMP-9, MMP-12, FGFR-4, FGF-3, and FGF-7are associated () with RDS, defined as surfactant application within the first 24 hours after birth. One of them, inFGFR-4(rs1966265), is associated with both RDS () and BPD ().Conclusion. rs1966265 inFGF receptor 4is a possible genetic key variant in alveolar diseases of preterm newborns.