Abstract
BACKGROUND: SFTPB expression (>25% normal) is necessary for the successful fetal-neonatal pulmonary transition.
OBJECTIVE: To determine if variants in SFTPB contribute to the risk of RDS in newborns.
METHODS: Using amplified genomic DNA and high throughput, automated sequencing, we genotyped promoter, all translated exons and intervening introns (8.5 kB) of SFTPB in 3 cohorts: 1) anonymous Guthrie cards from the Missouri Newborn Screening Program (Missouri cohort, n=1,116; 18% Black, 79% White), 2) newborns with RDS (RDS cohort, n=204; 40% Black, 59% White), and 3) newborns without lung disease (Control cohort, n=86, 51% Black, 45% White). We used PHASE V2.1, a Bayesian-based haplotype inference program, to computationally reconstruct race and gestational age-specific haplotypes in the RDS and Control cohorts using variant alleles that were present in >5% of the population.
RESULTS: We identified 119 polymorphic sites in SFTPB, including 17 exonic SNPs (10 nonsynonymous) and 5 intronic insertions or deletions. Of the other 97 intronic SNPs, 4 may impact RNA splicing by altering intron-exon junctions. The 121ins2 insertion, the common mutation associated with SP-B deficiency, was identified in 4 heterozygous individuals in the Missouri cohort. Based on Ewens predicted allele frequency, we have identified >99% of the SNPs with predicted frequencies of >0.001 in the Missouri cohort, and 92% in the NICU cohort. Despite the difference in cohort size, we found 17 rare (<4 heterozygous individuals) SNPs in the NICU cohort not detected in the Missouri cohort. There were significant differences in haplotype frequencies between the RDS and Control groups for all race and gestational age cohorts (P=0.01 to 0.05).
CONCLUSIONS: Rare variants contribute approximately 50% of genetic variation in the SFTPB. Rare, private variants and haplotypes are overrepresented in patients with RDS. Genetic variation in the SFTPB contributes to risk of RDS in infants.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hamvas, A., Wegner, D., Trusgnich, M. et al. 167 Variation in the Surfactant Protein B Gene (SFTPB) Contributes to Newborn Respiratory Distress (RDS). Pediatr Res 58, 383 (2005). https://doi.org/10.1203/00006450-200508000-00196
Issue Date:
DOI: https://doi.org/10.1203/00006450-200508000-00196