The study of relationships between β-globin gene mutations in β-thalassaemia patients, in response to hydroxyurea treatment

Background and

β-thalassaemia is the most frequent inherited disorder in the world, especially in Iran and Mazandaran Province. It is caused by mulation in β-globin gene on chromosome 11 with more than 150 different mulations causing β-thalassaemia, has been identified in the β-globin gene to date. Hydroxyurea, is one of the drugs used in Thalassemia patient’s treatment, however, it is not effective in all patients. The mechanisms of the hydroxyuea effect in not clear yet. This study compared different β-globin gene mutations in β-thalassaemia patients who were referred to the Thalassemia Research Center in Sari in two groups, good responder and non-responder, to the hydroxyurea.

This was a case-control study, comparing two groups of 30 thalassaemic patients who received hydroxyurea. Two groups were included, 30 good responders to hydroxyurea treatment (control) and 30 who did not respond to the treatment (case). First, DNA was extracted from peripheral blood. Then, two different methods for mutation detection were used. In the Thalassaemia Research Center in Sari, mutations in 60 patients were identified using ARMS-PCR. Also the results were confirmed in Genetic laboratory of Amirkola, using two mutation detection methods, reverse-dot blot hybridization and ARMS-PCR.

In the group of good responder (control), the average patient’s age were 28/1 ± 7/78 years, and the average age at the onset of blood transfusion was reported to be 8/5 ± 8/56 year. In this group, the mean comparison of the hemoglobin level and red blood size (MCV) prior and after drug consumption were statistically significant. In the group of non-responder (case), the mean age was 21.3 ± 6.43, the mean age starting blood transfusions was 3.3 ± 3.75, and the mean of drug consumption was 2.3 ± 0.8 months. From the mutations identified, IVSII-1G>A was the most common type in both case and control group, while of 30 of control group, 22 individuals were homozygous, and 7 individuals were heterozygous for this mutation (frequency % 42.5). For the 30 case patients, 11 individuals were homozygous, while 11 were heterozygous (frequency % 27.5). Comparison between two groups, case and control group, were statistically significance (P<0.008).

The correlations of IVSII-1G>A mutation in good responder patients to hydroxyurea as compared to the non responder group, is significant and similar to the previous findings.