Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease

A fundamental question in human biology and for hematological disease is how do complex gene-environment interactions lead to individual disease outcome? This is no less the case for sickle cell disease (SCD), a monogenic disorder of Mendelian inheritance, both clinical course, severity, and treatment response, is variable amongst affected individuals. New insight and discovery often lie between the intersection of seemingly disparate disciplines. Recently, opportunities for space medicine have flourished and have offered a new paradigm for study. Two recent Nature papers have shown that hemolysis and oxidative stress play key mechanistic roles in erythrocyte pathogenesis during spaceflight. This paper reviews existing genetic and environmental modifiers of the sickle cell disease phenotype. It reviews evidence for erythrocyte pathology in microgravity environments and demonstrates why this may be relevant for the unique gene-environment interaction of the SCD phenotype. It also introduces the hematology and scientific community to methodological tools for evaluation in space and microgravity research. The increasing understanding of space biology may yield insight into gene-environment influences and new treatment paradigms in SCD and other hematological disease phenotypes.