XmnI polymorphism : relation to b-thalassemia phenotype and genotype in Egyptian children

الملخص EN

Background : b-Globin mutations with Xmn1 site might be associated with elevated HbF expression which may in turn ameliorate the severity of b-thalassemia phenotype.

Aim of the study : To investigate the frequency of 158 (C > T) XmnI polymorphism among Egyptian Children and young adults with b-thalassemia, to examine the relationship between XmnI polymorphism and b-thalassemia genotypes and phenotypes and to assess the possible relation of XmnI polymorphism and response to hydroxyurea (Hu) therapy.

Patients and methods : Seventy-two b-thalassemia patients (37 females; M/F ratio 0.95) with a mean age of 7.53 ± 6.99 were included.

Laboratory investigations included Complete blood count (CBC), Hb electrophoresis by high performance liquid chromatography (HPLC), b-thalassemia mutation identification by the reverse dot blot hybridization technique (RDB) and detection of XmnlGg polymorphism by RFLP.

Results : The frequency of positive heterozygote XmnI gene polymorphism was 8.3%.

Eightythree percent of XmnIGc+/ patients were never transfused (p= 0.001) and had higher total hemoglobin compared to XmnIGc/ (p= 0.01); while mean HbF was higher among XmnIGc+/ patients compared to the other group but the difference was marginally insignificant (p=0.06).

b-Thalassemia mutation IVS II-1 showed relatively higher XmnI polymorphism frequency (50 %) and followed by its frequency among 10 undefined b-thalassemia mutations which was 20%.

The frequency of positive heterozygote XmnI gene polymorphism was 11.6% among the TI group vs.

3.5% among the TM group (p= 0.4).

Among 20 cases who received HU; 5/14 responders vs.

1/ 6 none responder had positive heterozygote XmnI gene polymorphism (p= 1.0).

Conclusions and recommendations : In conclusion, molecular determination of genetic markers in childhood will help to identify phenotypes of our patients and to avoid over or under treatment strategies.

Further prospective studies concerning the genetic markers that could predict the response to hemoglobin F inducers like hydroxyurea are highly recommended.