Prevalence study and molecular characterization of α-thalassemia in Filipinos

Abstract

 In order to determine the prevalence and molecular basis of α-thalassemia (thal) among Filipinos, a total of 2954 Filipinos in Taiwan were enrolled in this study. A complete blood count was done for every subject. Those with microcytosis (MCV less than 82.5 fl) were studied with hemoglobin (Hb) high-performance liquid chromatography to determine the levels of Hb A2 and Hb F, and with an enzyme immunoassay to determine plasma ferritin levels. Those who had microcytosis and normal or low levels of Hb A2 and Hb F were further studied with molecular methods for α-globin gene mutations. We used Southern blot hybridization and/or the polymerase chain reaction to detect Southeast Asian deletion, Filipino deletion, rightward and leftward single α-globin gene deletions, and Hb Constant Spring and Hb Quong Sze. Specific amplification and direct DNA sequencing of the α2- and α1-globin genes were carried out in apparent α-thal carriers without any of the above-mentioned mutations. Our results showed that in Filipinos the prevalence of α-thal 1 was 5% (147 carriers) and that of α-thal 2 was 1.7% (49 carriers); two had Hb H disease. Among the α-thal 1 carriers, 89 had the Southeast Asian deletion and 58 had the Filipino deletion. Among the α-thal 2 carriers, 48 had a rightward deletion and one had a leftward deletion. None had Hb Constant Spring or Hb Quong Sze. Specific amplification and DNA sequencing in five apparent α-thal carriers did not reveal mutations in the 2-kb region spanning the α2- and α1-globin genes. The molecular defects of α-thal in Filipinos were different from those in the neighboring ethnic groups. Elucidation of the α-thal mutations in Filipinos is useful in the genetic counseling and prenatal diagnosis of this common disease.