Genetic modifiers in hemoglobinopathies

Hereditary anemias show considerable variation in their clinical presentation. In some cases, the causes of these variations are easily apparent. In thalassemia (or in HbE/thalassemia), genetic variation is primarily caused by the severity of the thalassemia mutation. However, not uncommonly, there is variation unexplained by the globin gene mutations themselves, which may be caused by genetic modifiers. In sickle cell disease, the primary mutation is the same in all patients. Therefore, variations in disease severity generally are due to genetic modifiers. In most genetic diseases involving beta globin, the most clearcut influence on phenotype results from elevated fetal hemoglobin levels. In addition, alpha globin gene number can influence disease phenotype. In thalassemia major or intermedia, reduction in the number of alpha globin genes can ameliorate the disease phenotype; conversely, excess alpha globin genes can convert beta thalassemia trait to a clinical picture of thalassemia intermedia. In sickle cell disease, the number of alpha globin genes has both ameliorating and exacerbating effects, depending on which disease manifestation is being examined. Unlinked genetic factors have substantial effects on the phenotype of hereditary anemias, both on the anemia and other disease manifestations. Recently, studies using genome-wide techniques, particularly studying QTLs causing elevated HbF, or affecting HbE/thalassemia, have revealed other genetic elements whose mechanisms are under study. The elucidation of genetic modifiers will hopefully lead to more rational and effective management of these diseases.     

Rapid separation of human globin chains in normal and thalassemia patients by RP-HPLC

The present study describes a rapid and sensitive high-performance liquid chromatography (HPLC) method for the detection of human globin chains in blood. The method involves direct injection of globin chains which prepared by a standard method onto a micro bondapack C18 reversed-phase column (7.8 mm I.D.) with UV detection at 280 nm. The detection limit of hemoglobin (Hb) was 0.1 μg, which is equivalent to about 1 ml of fresh whole blood. We report here the rapid procedure for globin chain analysis. The present method will be useful for the determination of globin chain analysis in clinical laboratories, as well as in thalassemia and sickle cell disease patients.