A point of view: quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model.
The high degree of similarity at the molecular level, between humans and other species, has provided the rationale for the use of a variety of species as model systems in research, resulting in enormous advances in biological sciences and medicine. In contrast, the individual variability observed among humans, for example, in external physique, organ functionality and others, is accounted for, by only a fraction of 1% of differences at the DNA level. These small differences, which are essential for understanding disease pathogenesis, have posed enormous challenges in medicine, as we try to understand why patients may respond differently to drugs or why one patient has complications and another does not. Differences in outcome are most likely the result of interactions among genetic components themselves and/or the environment at the molecular, cellular, organ, or organismal level, or the macroenvironment. In this paper: (1) we consider some issues for multifactorial disease pathogenesis; (2) we provide a review of human SP-A and how the knowledge gained and the characteristics of the hSP-A system may serve as a model in the study of disease with multifactorial etiology; and (3) we describe examples where hSP-A has been used in the study of disease.
Floros
J
J
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, H166, Hershey, PA 17033-0850, USA. jfloros@psu.edu
Wang
G
G
D000483:Alleles; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D011510:Proteolipids / Q000235:genetics* / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000502:physiology*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics / Q000503:physiopathology; D014376:Tuberculosis / Q000235:genetics / Q000503:physiopathology
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants