Sex and Race Differences in Gene Expression in the Developing Human Lung Related to the Pathogenesis of Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a type of respiratory distress affecting newborn infants that differs in susceptibility and severity among different sexes and races. Current knowledge on BPD treatment is outdated due to recent changes in pathology and the heterogeneity of the disease, so understanding which methods are best suited for the infant given their physical and histological characteristics can prevent further lung trauma and accelerate recovery. Male and Caucasian infants are more likely to be diagnosed with BPD than females and infants of other racial groups and tend to require more intensive forms of treatment, implying genetic differences. Recent work in this field has identified overrepresented genes in BPD pathogenesis related to lung development. To identify which of these genes exhibited statistically significant differences between the sexes and races, differential expression analysis was performed on healthy fetal lung tissues. Overall, there were no significant differences in gene expression between the sexes. However, ADAMTS1 and ADAMTS5 were on average more highly expressed in male lungs while LTBP4 was on average more highly expressed in female lungs. There were also no significant differences in gene expression between the races. Still, BMP4 and TEK were on average more highly expressed in Caucasian lungs while PDGFD and PDGFRA were on average more highly expressed in African American lungs. These seven genes play important roles in the assembly and degradation of the extracellular matrix, formation of elastic fibers, and PDGF signaling pathways, indicating that there are subtle sex and race differences that can greatly impact lung development, even in healthy individuals. This thesis identifies genetic targets in abnormal lung development related to sex and race and new focuses for research into BPD diagnostics and prevention.