Abstract
Introduction: Elevated HbA(2) (hemoglobin A(2)) level is considered the most reliable hematological parameter for the detection of beta-thalassemia carriers. However, some carriers are difficult to recognize because the level of HbA(2) is not in the distinctive carrier range, i.e. 4.0-6.0%; instead, some carriers have HbA(2) levels between normal and carrier levels, i.e. borderline HbA(2) (HbA(2) = 3.1-3.9%). Studies have shown that variations in the erythroid Kruppel-like factor (KLF1) gene lead to borderline HbA(2) in beta-thalassemia carriers from various populations. The incidence of borderline HbA(2) in Saudis is high.
Material and methods: To confirm the influence of variations in KLF1, HBA1, HBA2 and HBB genes for the reduction of the level of HbA(2) in Saudi beta-thalassemia carriers, we performed a direct sequence analysis of KLF1, HBA1, HBA2 and HBB genes from 212 healthy Saudis (88 subjects: HbA(2) < 3; 72 subjects: HbA(2) = 3.1 to 3.9; 52 subjects HbA(2) > 4.3).
Results: The presence of the borderline HbA(2) level is not specific to any type of beta-thalassemia variation or beta(+)-thalassemia variations in Saudis. Two exonic (c.304T>C and c.544T>C) and two 3' untranslated region (3'UTR) (c.(star)296G>A and c.(star)277C>G) variations have been identified in the KLF1 gene for the first time from an Arab population. None of these four variations in KLF1 genes are significantly associated with the Saudis with borderline HbA(2). alpha Globin genotype, -alpha(2) (3.7)/alpha(1)alpha(2), is found to be the most frequent(55.55%) among healthy Saudis with borderline HbA(2) compared with the other groups (HbA(2) < 3 = 20.45%; HbA(2) > 4.3 = 13.51%).
Conclusions: Further studies are necessary to determine the influence of other factors on the presence of borderline HbA(2) in 41.67% of Saudis.