Known and potential sources for epistatic effects in sickle cell anemia

R. L. Nagel, M. E. Fabry, D. K. Kaul, Henny H. Billett, H. Croizat, D. Labie, M. Canessa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The enormous variation in the clinical expression within each sickle cell syndrome (SS, SC, S/β thalassemia) strongly suggests that genetic factors (epistatic effects) are at play in modulating the intensity of individual clinical components that form the overall clinical syndrome. These epistatic effects need not affect all clinical components equally: red cell genetic modifiers are likely to affect those aspects of the clinical syndrome that are mostly determined by red cell polymerization-dependent pathophysiology: hemolysis in the first place and all those organ damages in which there is evidence that they are correlated with the patients' HbF levels (leg ulcers, aseptic necrosis, retinal changes, etc.). In these cases, the regulation of the level of HbF response to anemia and the cation transport systems involved in red cell volume regulation may be paramount. On the other hand, there are clinical elements in sickle cell anemia that are predominantly modulated by nonpolymerization-dependent red cell factors (as for example red cell/endothelium interactions) or entirely non-red-cell factors (microvascular regulation). The corresponding epistatic effects, in this case, will be found in a variety of sources: synthesis and regulation of receptors and integrins involved in red cell adhesion to the endothelium, regulation of perfusion pressure, regulation of vascular tone and diameter, etc. It will be the challenge of the next decade to identify and quantitate them if we are to fully understand the pathophysiology of sickle cell anemia and its phenotypic variability.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume565
StatePublished - 1989
Externally publishedYes

Fingerprint

Sickle Cell Anemia
Cells
Endothelium
Pressure regulation
Leg Ulcer
Thalassemia
Cell adhesion
Hemolysis
Cell Size
Cell Adhesion
Integrins
Cell Communication
Polymerization
Blood Vessels
Cations
Anemia
Necrosis
Perfusion
Sickles
Pressure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagel, R. L., Fabry, M. E., Kaul, D. K., Billett, H. H., Croizat, H., Labie, D., & Canessa, M. (1989). Known and potential sources for epistatic effects in sickle cell anemia. Annals of the New York Academy of Sciences, 565, 228-238.

Known and potential sources for epistatic effects in sickle cell anemia. / Nagel, R. L.; Fabry, M. E.; Kaul, D. K.; Billett, Henny H.; Croizat, H.; Labie, D.; Canessa, M.

In: Annals of the New York Academy of Sciences, Vol. 565, 1989, p. 228-238.

Research output: Contribution to journalArticle

Nagel, RL, Fabry, ME, Kaul, DK, Billett, HH, Croizat, H, Labie, D & Canessa, M 1989, 'Known and potential sources for epistatic effects in sickle cell anemia', Annals of the New York Academy of Sciences, vol. 565, pp. 228-238.
Nagel, R. L. ; Fabry, M. E. ; Kaul, D. K. ; Billett, Henny H. ; Croizat, H. ; Labie, D. ; Canessa, M. / Known and potential sources for epistatic effects in sickle cell anemia. In: Annals of the New York Academy of Sciences. 1989 ; Vol. 565. pp. 228-238.
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