title: Identification and examination of a novel 9-bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid-acute lung injury model.
abstract: The pulmonary surfactant-associated protein (SFTPA1, SP-A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR-single-strand conformation polymorphism method, a novel 9-bp nucleotide insertion (+) or deletion (-) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (-/-, +/- and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)-ALI model by 1-h and 3-h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9-bp indel polymorphism (P < 0.01). The lung water content of the OA injection group was markedly higher than that of the control group and lung water content for the +/+ genotype was significantly higher than that of the others in the 1-h group (P < 0.01). No differences in the expression of the SFTPA1 gene were found among individuals with different SFTPA1 genotypes, indicating that the trait is not caused by a linked polymorphism causing altered expression of the gene. The individuals with the -/- genotype showed lower lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease-resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies.
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Yuebo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Longchao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Han Dan College, Handan, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Kebin
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D005091:Exons; D015633:Extravascular Lung Water / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D016254:Mutagenesis, Insertional; D019301:Oleic Acid / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000235:genetics*; D013552:Swine
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D037662:Pulmonary Surfactant-Associated Protein A; C445842:SFTPA1 protein, human; D019301:Oleic Acid
keywords: OA-ALI model; SFTPA1 gene; acute lung injury; indel polymorphism; pig