Blood groups: genetics and physiology

摘要

Numerous studies in biochemistry, genetics and molecular biology conducted over two decades have shown that blood group gene products expressed on red cells and various tissues exhibit a variety of potential functions, which can be schematically classified into functional groups such as transporters and channels, receptors, adhesion molecules, enzymes or structural components, with a further level of complexity as a same molecule may exhibit multiple functions. As structures present on red cells, blood group and blood group-related molecules may contribute to the structure and function of the red cell membrane and may help to clarify unresolved biological processes (for instance, water and gas transport through biological membranes). Alternatively, some of these molecules may simply be the witnesses of a residual persistence of membrane components during erythroid cell differentiation with no significant function. Investigation of blood group and blood group-related molecules as structures present on epithelial or endothelial cells of tissues and organs has revealed other features of their potential physiological role and led to the discovery of some unexpected functions (for instance Fy-mediated transcy-tose). Increasing our knowledge on both aspects is of interest not only for transfusion medicine, but also for transplantation and for understanding the normal physiology and physiopathology of several diseases. Current studies indicate that blood group and blood group-related molecules cover large areas of human physiology from cerebral to renal and reproduction biology. As specific deficiencies of these molecules have only a minor or no detrimental effect in most instances, they are either dispensable for cell function or redundant. In some instances, however, a function becomes apparent under stress or in pathological conditions. How common and rare blood group polymorphisms are maintained and may impact function is largely unknown, although a few examples clearly point to selective pressure exerted by pathogenic micro-organisms. Despite significant progress, much remains to be discovered to clearly delineate how blood group molecules, alone or as molecular complexes in erythroid and non-erythroid cells, may act in health and disease, to understand the underlying mechanisms, and, ultimately, how these findings might eventually be translated into clinical applications.