Prevalence study and molecular characterization of α-thalassemia in Filipinos

Abstract

In order to determine the prevalence and molecular basis of alpha-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 alpha-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 alpha-globin gene deletions, and Hb Constant Spring and Hb Quong Sze. Specific amplification and direct DNA sequencing of the alpha2- and alpha1-globin genes were carried out in apparent alpha-thal carriers without any of the above-mentioned mutations. Our results showed that in Filipinos the prevalence of alpha-thal 1 was 5% (147 carriers) and that of alpha-thal 2 was 1.7% (49 carriers); two had Hb H disease. Among the alpha-thal 1 carriers, 89 had the Southeast Asian deletion and 58 had the Filipino deletion. Among the alpha-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 alpha-thal carriers did not reveal mutations in the 2-kb region spanning the alpha2- and alpha1-globin genes. The molecular defects of alpha-thal in Filipinos were different from those in the neighboring ethnic groups. Elucidation of the alpha-thal mutations in Filipinos is useful in the genetic counseling and prenatal diagnosis of this common disease.

Microcytic hypochromic anemia patients with thalassemia : Genotyping approach

“…Our Þ ndings are in concordance with previous reports, where microcytosis was explained on the basis of α-gene number. [3,[19][20][21][22] The identiÞ cation of α-and β-thalassemia carrier status is important to prevent erroneous and expensive investigations to define the etiology of anemia, as well as prevent unnecessary prolonged iron supplementation. The knowledge of α-and β-gene numbers in α-and β-thalassemia traits in any population is necessary, as it modifies the phenotype of thalassemia by altering the ratio of α-and β-chains of hemoglobin.…”

“…The double α-gene deletions in cis, such as the --SEA, --FIL and -THAI, are most common in Southeast Asia, while the --MED and the --20.5 double-gene deletions occur most frequently in the Mediterranean area. [3] Inheritance of 2 functional gene deletions such as -MED is very rare, especially in our area. We could determine many cases that show these mutations in our study.…”

“…There is limited data reported in the literature for prevalence of α-gene deletion in patients with microcytosis. [3,4] Carriers of α-gene deletion have mild microcytosis with or without anemia. Although anemia is absent or unremarkable, it is important to diagnose α-thalassemia in order to diagnose the cause of microcytosis and to avoid repeated expensive analysis and/ or prolonged iron therapy.…”

The Hemoglobin O mutation in Indonesia: distribution and phenotypic expression

“…The reduced production of α-globin chain in α-thalassemia would give the α OIna -globin chains a higher probability of forming HbO. We have tested both UP-1015 and KJG-16 for the Southeast Asian α-globin gene deletion, which accounts for approximately 90% of the α-thalassemia mutations in the neighboring Southeast Asian countries (Ko et al 1999). The mutation could not be detected in these two cases, but the possibility of other α-globin defects still cannot be discounted.…”

The effect of a school-based weekly iron supplementation delivery system among anemic schoolchildren in the Philippines

“…However, a prevalence survey of Filipinos living in Taiwan showed a 5% prevalence for a-thalassemia 1 trait, 1.7% for a-thalassemia 2 trait (Koh et al, 1998) and 4% for bthalassemia trait (Koh et al, 1999). The study participants were not screened for thalassemia, and it is thus possible that some children were carriers of the thalassemia genes.…”