Hematologic Phenotype of the Mutations Ivs1-n6 (T →. C), lVS1-n110 (C → A), AND CD39 (C → T) IN CARRIERS OF P-THALASSEMIA IN GREECE

Abstract

The hematologic phenotype was characterized in heterozygotes for three of the most common β-thalassemia mutations in the Greek population. The study included 17 carriers of β^{+ +} IVSl-n6 (T → C), 21 carriers of β⁺ IVS1-nl10 (G → A), and 17 carriers of β^± CD39 (C → T). The 55 β-thalassemia heterozygotes were selected from among parents of patients on regular transfusion regimns, and the β-thalassemia mutation was identified by means of the polymerase chain reaction to amplify the appropriate regzon of the β-globin gene and then by allele-specific oligonucleotide hybridization. The assessment of hematologic phenotype included complete blood count and quantitation of hemoglobin HbA₂ and HbF and of the globin chain biosynthesis ratio. Comparison and statistical analysis of the hematologic parameters for the three mutations demonstrated no consistent correlation among the three mutations relative to Hb levels, hematocrit, and red cell indices, although heterozygotes for the IVS1-n6 mutation produce red blood cells with slightly higher mean corpuscular volume; significantly lower values of HbA₂ (mean, 3.81% ± 0.62% with four values less than 3.60%) in IVS1-n6 heterozygotes compared with IVS1-n110 heterozygotes (mean, 4.69% ± 0.48%) and CD39 heterozygotes (mean, 4.75% ± 0.50%, P < 0.001); and signafcantly higher HbF levels in CD39 heterozygotes (mean, 2.31% ± 1.52%) compared with IVS1-n6 heterozygotes (mean, 0.79% ± 0.45%, P < 0.01) and IVS1-n110 heterozygotes (mean, 1.17% ± 0.75%, P < 0.01). With respect to the HbA₂ levels, the findings are in agreement with previous studies in Mediterranean populations; the slightly higher levels of HbF in CD39 heterozygotes appear to be reported for the first time.

Key Words:

• β-thalassemia mutations
• hematologic phenotype
• heterozygous β-thal-assemia