Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis
Surfactant proteins (SP) are involved in surfactant function and innate immunity in the human lung. Both lung function and innate immunity are altered in CF, and altered SP levels and genetic association are observed in Cystic Fibrosis (CF). We hypothesized that single nucleotide polymorphisms (SNPs...
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02256/full |
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| author | Zhenwu Lin Nithyananda Thorenoor Rongling Wu Susan L. DiAngelo Meixia Ye Meixia Ye Neal J. Thomas Xiaojie Liao Tony R. Lin Stuart Warren Joanna Floros Joanna Floros |
| author_facet | Zhenwu Lin Nithyananda Thorenoor Rongling Wu Susan L. DiAngelo Meixia Ye Meixia Ye Neal J. Thomas Xiaojie Liao Tony R. Lin Stuart Warren Joanna Floros Joanna Floros |
| author_sort | Zhenwu Lin |
| collection | DOAJ |
| description | Surfactant proteins (SP) are involved in surfactant function and innate immunity in the human lung. Both lung function and innate immunity are altered in CF, and altered SP levels and genetic association are observed in Cystic Fibrosis (CF). We hypothesized that single nucleotide polymorphisms (SNPs) within the SP genes associate with CF or severity subgroups, either through single SNP or via SNP-SNP interactions between two SNPs of a given gene (intragenic) and/or between two genes (intergenic). We genotyped a total of 17 SP SNPs from 72 case-trio pedigree (SFTPA1 (5), SFTPA2 (4), SFTPB (4), SFTPC (2), and SFTPD (2)), and identified SP SNP associations by applying quantitative genetic principles. The results showed (a) Two SNPs, SFTPB rs7316 (p = 0.0083) and SFTPC rs1124 (p = 0.0154), each associated with CF. (b) Three intragenic SNP-SNP interactions, SFTPB (rs2077079, rs3024798), and SFTPA1 (rs1136451, rs1059057 and rs4253527), associated with CF. (c) A total of 34 intergenic SNP-SNP interactions among the 4 SP genes to be associated with CF. (d) No SNP-SNP interaction was observed between SFTPA1 or SFTPA2 and SFTPD. (e) Equal number of SNP-SNP interactions were observed between SFTPB and SFTPA1/SFTPA2 (n = 7) and SP-B and SFTPD (n = 7). (f) SFTPC exhibited significant SNP-SNP interactions with SFTPA1/SFTPA2 (n = 11), SFTPB (n = 4) and SFTPD (n = 3). (g) A single SFTPB SNP was associated with mild CF after Bonferroni correction, and several intergenic interactions that are associated (p < 0.01) with either mild or moderate/severe CF were observed. These collectively indicate that complex SNP-SNP interactions of the SP genes may contribute to the pulmonary disease in CF patients. We speculate that SPs may serve as modifiers for the varied progression of pulmonary disease in CF and/or its severity. |
| first_indexed | 2024-04-14T02:45:20Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-14T02:45:20Z |
| publishDate | 2018-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-1420dd4700b74a4485fc3f2fec8a1efb2022-12-22T02:16:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02256404123Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic FibrosisZhenwu Lin0Nithyananda Thorenoor1Rongling Wu2Susan L. DiAngelo3Meixia Ye4Meixia Ye5Neal J. Thomas6Xiaojie Liao7Tony R. Lin8Stuart Warren9Joanna Floros10Joanna Floros11Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesPublic Health Science, College of Medicine, Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesPublic Health Science, College of Medicine, Pennsylvania State University, Hershey, PA, United StatesCenter for Computational Biology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, ChinaDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University, Hershey, PA, United StatesObstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, PA, United StatesSurfactant proteins (SP) are involved in surfactant function and innate immunity in the human lung. Both lung function and innate immunity are altered in CF, and altered SP levels and genetic association are observed in Cystic Fibrosis (CF). We hypothesized that single nucleotide polymorphisms (SNPs) within the SP genes associate with CF or severity subgroups, either through single SNP or via SNP-SNP interactions between two SNPs of a given gene (intragenic) and/or between two genes (intergenic). We genotyped a total of 17 SP SNPs from 72 case-trio pedigree (SFTPA1 (5), SFTPA2 (4), SFTPB (4), SFTPC (2), and SFTPD (2)), and identified SP SNP associations by applying quantitative genetic principles. The results showed (a) Two SNPs, SFTPB rs7316 (p = 0.0083) and SFTPC rs1124 (p = 0.0154), each associated with CF. (b) Three intragenic SNP-SNP interactions, SFTPB (rs2077079, rs3024798), and SFTPA1 (rs1136451, rs1059057 and rs4253527), associated with CF. (c) A total of 34 intergenic SNP-SNP interactions among the 4 SP genes to be associated with CF. (d) No SNP-SNP interaction was observed between SFTPA1 or SFTPA2 and SFTPD. (e) Equal number of SNP-SNP interactions were observed between SFTPB and SFTPA1/SFTPA2 (n = 7) and SP-B and SFTPD (n = 7). (f) SFTPC exhibited significant SNP-SNP interactions with SFTPA1/SFTPA2 (n = 11), SFTPB (n = 4) and SFTPD (n = 3). (g) A single SFTPB SNP was associated with mild CF after Bonferroni correction, and several intergenic interactions that are associated (p < 0.01) with either mild or moderate/severe CF were observed. These collectively indicate that complex SNP-SNP interactions of the SP genes may contribute to the pulmonary disease in CF patients. We speculate that SPs may serve as modifiers for the varied progression of pulmonary disease in CF and/or its severity.https://www.frontiersin.org/article/10.3389/fimmu.2018.02256/fullsurfactant proteinSP-ASP-BSP-CSP-Dcystic fibrosis |
| spellingShingle | Zhenwu Lin Nithyananda Thorenoor Rongling Wu Susan L. DiAngelo Meixia Ye Meixia Ye Neal J. Thomas Xiaojie Liao Tony R. Lin Stuart Warren Joanna Floros Joanna Floros Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis Frontiers in Immunology surfactant protein SP-A SP-B SP-C SP-D cystic fibrosis |
| title | Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis |
| title_full | Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis |
| title_fullStr | Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis |
| title_full_unstemmed | Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis |
| title_short | Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis |
| title_sort | genetic association of pulmonary surfactant protein genes sftpa1 sftpa2 sftpb sftpc and sftpd with cystic fibrosis |
| topic | surfactant protein SP-A SP-B SP-C SP-D cystic fibrosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02256/full |
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