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Current Pharmacogenomics
ISSN (Print): 1570-1603
ISSN (Online): 1570-1603
DOI: 10.2174/1570160054022935      Price:  $58

Genetic Diversity of Human SP-A, a Molecule with Innate host Defense and Surfactant-Related Functions; Characteristics, Primary Function, and Significance

Author(s): Joanna Floros, Guirong Wang and Zhenwu Lin
Pages 87-95 (9)
Pulmonary surfactant, a lipoprotein complex, is essential for life. It lowers the surface tension at the air-liquid interphase of the distal lung airspaces (alveoli) to prevent alveolar collapse at low lung volumes. Alveolar stability is critical in maintaining a normal O2/CO2 exchange. Surfactant deficiency in the prematurely born infant can lead to respiratory problems or respiratory distress syndrome (RDS); a major complication of infants with RDS is infection. Surfactant dysfunction has been associated with several pulmonary diseases characterized with impaired O2/CO2 exchange, deranged inflammatory processes and host defense. Pulmonary surfactant consists of approximately 90% lipids, with phospholipids constituting the major lipid component, and about 10% of proteins with surfactant protein A (SP-A) found in great abundance. SP-A has been identified with several diverse functions. Broadly, these include surfactantrelated and host defense-related functions. Human SP-A is encoded by two genes, SP-A1 and SP-A2, and exhibits extensive complexity at the DNA, RNA, and protein level, compared to rodent SP-A and even to that of the primates. Although, the significance of such complexity is not currently understood, a number of studies have revealed associations between certain SP-A variants or levels of SP-A and pulmonary disease. Moreover, functional, structural, and biochemical differences have been observed between in vitro expressed SP-A1 and SP-A2 variants. We speculate that the human SP-A complexity provides diversity in the overall SP-A functional activities. We suggest that because of its complexity, which appears to translate in quantitative and qualitative differences among individuals, SP-A can provide a good model for study of the basis of individual variability to disease susceptibility and/or to drug response. In this paper, we review types of SP-A complexity and comment on the significance of such variability, summarize associations between SP-A genetic variants and pulmonary diseases, and speculate on the SP-A primary function (surfactant or the host defense) by discussing a number of attributes. The focus of this mini review is on the human SP-A genes and alleles.
gene duplication, single nucleotide polymorphisms (snps), sequence variability, pseudogene, carbohydrate recognition domain (crd), innate immunity, pulmonary surfactant
Department of Cellular and Molecular Physiology, H166, The Pennsylvania State University College ofMedicine, 500 University Drive, Hershey, PA 17033, USA.