The Common Haplotype GATGACA in Surfactant-Protein B Gene Is Protective for Respiratory Distress Syndrome in Preterm Neonates

Silvia Mikolajcikova; Zora Lasabova; Veronika Holubekova; Maria Skerenova; Jana Zibolenova; Katarina Matasova Sr; Mirko Zibolen; Andrea Calkovska

doi:10.3389/fped.2022.851042

The Common Haplotype GATGACA in Surfactant-Protein B Gene Is Protective for Respiratory Distress Syndrome in Preterm Neonates

Front Pediatr. 2022 May 25:10:851042. doi: 10.3389/fped.2022.851042. eCollection 2022.

Authors

Silvia Mikolajcikova¹, Zora Lasabova², Veronika Holubekova³, Maria Skerenova³, Jana Zibolenova⁴, Katarina Matasova Sr¹, Mirko Zibolen¹, Andrea Calkovska⁵

Affiliations

¹ Clinic of Neonatology, Jessenius Faculty of Medicine, Comenius University and University Hospital, Martin, Slovakia.
² Department of Molecular Biology and Genomics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
³ Biomedical Centre Martin, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
⁴ Department of Public Health, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
⁵ Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.

Abstract

Background: Respiratory distress syndrome (RDS), a disorder of primary surfactant deficiency resulting in pulmonary insufficiency, remains a significant problem for preterm neonates. Associations between genetic variants of surfactant proteins and RDS have been reported, but haplotypes of the surfactant protein B gene (SFTPB) have not been studied. The aim of the study was to prove the hypothesis that certain haplotypes of SFTPB may be protective or risk factors for RDS.

Methods: The study was performed with 149 preterm infants, born <34 weeks of gestation, with 86 infants with mild RDS or without RDS (control group) and 63 infants with severe RDS (patient group). RDS was considered severe if multiple doses of exogenous surfactant and/or mechanical ventilation within the first 72 h of life were needed. The venous blood sample was used for the analysis of gene polymorphisms associated with RDS, genotyping, and haplotype estimation. Multivariate logistic regression analysis and the odds ratio were calculated to detect the contribution of the studied variables to the development of RDS.

Results: A new association of the common single nucleotide polymorphism (SNP) rs2304566 with RDS in premature infants was detected. Analysis of rs2304566 polymorphisms using a logistic regression model showed that there are two significant predictors inversely related to the occurrence of RDS (Apgar score of 5 min, CT and TT genotype in rs2304566 polymorphism). Gestational age, birth weight, and sex have border significance. Moreover, in the patient group, the frequency of the GATGACA haplotype in the SFTPB gene was lower (p = 0.037), and the GATGGCA haplotype was higher (p = 0.059) in comparison with the control group.

Conclusion: The common haplotype GATGACA of the SFTPB gene can be protective against RDS in preterm infants. The trend of a higher frequency of GATGGCA in the SFTPB gene in infants with severe RDS suggests that this haplotype may be a risk factor for RDS susceptibility.

Keywords: SFTPB; haplotype; neonate; respiratory distress; surfactant.