Single Nucleotide Polymorphisms Interactions of the Surfactant Protein Genes Associated With Respiratory Distress Syndrome Susceptibility in Preterm Infants

Amatya, Shaili; Ye, Meixia; Yang, Lili; Gandhi, Chintan K.; Wu, Rongling; Nagourney, Beth A.; Floros, Joanna

doi:10.3389/fped.2021.682160

Cited by 8 publications

(19 citation statements)

References 100 publications

(114 reference statements)

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“…In fact, the pattern of SNPs and their interactions was unique to each disease population. For example, SNPs of the SFTPB and the SFTPC by themselves and/or through their interactions were significantly associated with cystic fibrosis ( Lin et al, 2018 ), whereas, SNPs of the SFTPA1 and SFTPA2 and their interactions were associated with an increased HP risk in a Mexican population ( Gandhi et al, 2021 ) and RDS in prematurely born neonates ( Amatya et al, 2021 ). The majority of the significant interactions associated with an increased ARF risk involved SFTPA2 SNPs, whereas the majority of the significant interactions associated with an increased risk of pulmonary dysfunction at discharge involved SFTPA1 SNP s in the same dataset ( Gandhi et al, 2020a ).…”

Section: Discussionmentioning

confidence: 99%

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children

Gandhi

Thomas

et al. 2022

Front. Genet.

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We studied associations of persistent respiratory morbidity (PRM) at 6 and 12 months after acute respiratory failure (ARF) in previously healthy children with single-nucleotide polymorphisms (SNPs) of surfactant protein (SP) genes. Of the 250 enrolled subjects, 155 and 127 were followed at 6 and 12 months after an ARF episode, respectively. Logistic regression analysis and SNP–SNP interaction models were used. We found that 1) in the multivariate analysis, an increased risk at 6 and 12 months was associated with rs1124_A and rs4715_A of SFTPC, respectively; 2) in a single SNP model, increased and decreased risks of PRM at both timepoints were associated with rs1124 of SFTPC and rs721917 of SFTPD, respectively; an increased risk at 6 months was associated with rs1130866 of SFTPB and rs4715 of SFTPC, and increased and decreased risks at 12 months were associated with rs17886395 of SFTPA2 and rs2243639 of SFTPD, respectively; 3) in a two-SNP model, PRM susceptibility at both timepoints was associated with a number of intergenic interactions between SNPs of the studied SP genes. An increased risk at 12 months was associated with one intragenic (rs1965708 and rs113645 of SFTPA2) interaction; 4) in a three-SNP model, decreased and increased risks at 6 and 12 months, respectively, were associated with an interaction among rs1130866 of SFTPB, rs721917 of SFTPD, and rs1059046 of SFTPA2. A decreased risk at 6 months was associated with an interaction among the same SNPs of SFTPB and SFTPD and the rs1136450 of SFTPA1. The findings revealed that SNPs of all SFTPs appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.

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Section: Discussionmentioning

confidence: 99%

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children

Gandhi

Thomas

et al. 2022

Front. Genet.

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“…In the SFTPB gene, there was one significant intragenic interaction (rs2077079, rs3024798, and rs7316). Each SNP exhibited a dominant effect, and this interaction was associated with a decreased risk of RDS ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although the incidence of RDS is inversely related to gestational age, preterm delivery alone does not determine the risk of developing the disorder. Several studies have suggested the possible involvement of surfactant protein (SP) SP-A2 and SP-B, SP-C, and SP-D common genetic polymorphisms in the genetic predisposition to RDS ( 2 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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BackgroundRespiratory 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.MethodsThe 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.ResultsA 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.ConclusionThe 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.

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“…This SNP-SNP interaction approach ( 57 ) has been used and validated in studying associations of high order epistatic interactions with various acute and chronic pulmonary diseases ( 21 , 47 , 58 , 59 ). The cases and controls were converted into a 2 × 2 contingency table and various types of epistatic interactions at different orders were tested.…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we used a statistical approach ( 57 ) where novel statistical models were studied to enable investigation of the epistatic effects of SNP-SNP interactions as has been done for other pulmonary diseases ( 21 , 47 , 58 , 59 ). Using this novel approach, we reanalyzed IPF data that were previously published.…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms (SNP) and SNP-SNP Interactions of the Surfactant Protein Genes Are Associated With Idiopathic Pulmonary Fibrosis in a Mexican Study Group; Comparison With Hypersensitivity Pneumonitis

Abbasi

Chen²,

Gandhi³

et al. 2022

Front. Immunol.

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Surfactant proteins (SPs) are important for normal lung function and innate immunity of the lungs and their genes have been identified with significant genetic variability. Changes in quantity or quality of SPs due to genetic mutations or natural genetic variability may alter their functions and contribute to the host susceptibility for particular diseases. Alternatively, SP single nucleotide polymorphisms (SNPs) can serve as markers to identify disease risk or response to therapies, as shown for other genes in a number of other studies. In the current study, we evaluated associations of SFTP SNPs with idiopathic pulmonary fibrosis (IPF) by studying novel computational models where the epistatic effects (dominant, additive, recessive) of SNP-SNP interactions could be evaluated, and then compared the results with a previously published hypersensitivity pneumonitis (HP) study where the same novel models were used. Mexican Hispanic patients (IPF=84 & HP=75) and 194 healthy control individuals were evaluated. The goal was to identify SP SNPs and SNP-SNP interactions that associate with IPF as well as SNPs and interactions that may be unique to each of these interstitial diseases or common between them. We observed: 1) in terms of IPF, i) three single SFTPA1 SNPs to associate with decreased IPF risk, ii) three SFTPA1 haplotypes to associate with increased IPF risk, and iii) a number of three-SNP interactions to associate with IPF susceptibility. 2) Comparison of IPF and HP, i) three SFTPA1 and one SFTPB SNP associated with decreased risk in IPF but increased risk in HP, and one SFTPA1 SNP associated with decreased risk in both IPF and HP, ii) a number of three-SNP interactions with the same or different effect pattern associated with IPF and/or HP susceptibility, iii) one of the three-SNP interactions that involved SNPs of SFTPA1, SFTPA2, and SFTPD, with the same effect pattern, was associated with a disease-specific outcome, a decreased and increased risk in HP and IPF, respectively. This is the first study that compares the SP gene variants in these two phenotypically similar diseases. Our findings indicate that SNPs of all SFTPs may play an important role in the genetic susceptibility to IPF and HP. Importantly, IPF and HP share some SP genetic variants, suggesting common pathophysiological mechanisms and pathways regarding surfactant biogenesis, but also some differences, highlighting the diverse underlying pathogenic mechanisms between an inflammatory-driven fibrosis (HP) and an epithelial-driven fibrosis (IPF). Alternatively, the significant SNPs identified here, along with SNPs of other genes, could serve as markers to distinguish these two devastating diseases.

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Single Nucleotide Polymorphisms Interactions of the Surfactant Protein Genes Associated With Respiratory Distress Syndrome Susceptibility in Preterm Infants

Cited by 8 publications

References 100 publications

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children

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

Single Nucleotide Polymorphisms (SNP) and SNP-SNP Interactions of the Surfactant Protein Genes Are Associated With Idiopathic Pulmonary Fibrosis in a Mexican Study Group; Comparison With Hypersensitivity Pneumonitis

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