Genetic Variants of Surfactant Proteins A, B, C, and D in Bronchopulmonary Dysplasia

Abstract

BPD_28D (O2 dependency at 28 days of life) and BPD_36W (O2 dependency at 36 wks post-menstrual age) are diseases of prematurely born infants exposed to mechanical ventilation and/or oxygen supplementation. In order to determine whether genetic variants of surfactant proteins (SPs-A, B, C, and D) and SP-B-linked microsatellite markers are risk factors in BPD, we performed a family based association study using a Greek study group of 71 neonates (<30 wks gestational age) from 60 families with, 52 BPD_28D and 19 BPD_36W, affected infants. Genotyping was performed using newly designed pyrosequencing assays and previously published methods. Associations between genetic variants of SPs and BPD subgroups were determined using Transmission Disequilibrium Test (TDT) and Family Based Association Test (FBAT). Significant associations (p ≤ 0.01) were observed for alleles of SP-B and SP-B-linked microsatellite markers, and haplotypes of SP-A, SP-D, and SP-B. Specifically, allele B-18_C associated with susceptibility in BPD_36W. Microsatellite marker AAGG_6 associated with susceptibility in BPD_28D/36W group. Haplotype analysis revealed ten susceptibility and one protective haplotypes for SP-B and SP-B-linked microsatellite markers and two SP-A-SP-D protective haplotypes. The data indicate that SP loci are linked to BPD. Studies in different study groups and/or of larger sample size are warranted to confirm these observations and delineate genetic background of BPD subgroups.

Genetic Risk Factors of Bronchopulmonary Dysplasia

“…It is very likely that genetic differences other than growth factor gene polymorphisms play a role in determining the risk of BPD. Genetic variation in surfactant protein genes may also influence the severity of respiratory distress syndrome and subsequent development of BPD (30,31). Polymorphisms in cytokines and their receptors, bacterial pattern recognition molecules, surfactant proteins, and heme oxygenase-1 are all known to alter the course of other pulmonary diseases in adults and children.…”

“…A prospective study was conducted in the Neonatal Intensive Care Unit of the Polish-American Children's Hospital between May 21, 2003 and October 31,2006. The entry criteria were: 1) preterm birth at 24 -32 wk gestational age; 2) birthweight Յ1500 g (VLBW); and 3) a need for mechanical ventilation or noninvasive respiratory support (nasal continuous positive airway pressure-nCPAP) during the first 3 d of life.…”

Genetics of bronchopulmonary dysplasia in the age of genomics

“…Interestingly, variable deletions of this CA-rich sequence lead to abnormal splicing of the SP-B mRNA, and possibly also abnormal protein expression in cell lines [31]. In another study, which included 71 infants with mild or moderate BPD, family-based tests were used to determine associations with microsatellite markers within the surfactant protein-A, B, C and D gene loci [32]. Several associations were detected in this study [32].…”

“…In another study, which included 71 infants with mild or moderate BPD, family-based tests were used to determine associations with microsatellite markers within the surfactant protein-A, B, C and D gene loci [32]. Several associations were detected in this study [32]. However, this study lacked sufficient details to evaluate potential population biases.…”

MicroRNA Expression Aberration Associated with Bronchopulmonary Dysplasia in Preterm Infants: A Preliminary Study

“…7,8 Although several association studies have examined the roles of genetic variants in inflammatory regulation and surfactant synthesis in BPD, the results have failed to show consistent associations. [9][10][11][12][13][14][15][16][17] In developmentally appropriate BPD animal models, altered expression levels of certain transcription factors for protein-coding RNA have been linked to alveolarization, angiogenesis, or remodeling of the lung extracellular matrix. [18][19][20][21][22] However, BPD pathogenesis in human infants remains incompletely understood.…”