ABSTRACT
beta-Globin mutations with Xmnl site might be associated with elevated HbF expression which may in turn ameliorate the severity of p-thalassemia phenotype. To investigate the frequency of -158 [C > T] Xmnl polymorphism among Egyptian Children and young adults with p-thalassemia, to examine the relationship between Xmnl polymorphism and p-thalassemia genotypes and phenotypes and to assess the possible relation of Xmnl polymorphism and response to hydroxyurea [Hu] therapy. Seventy-two P-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], p-thalassemia mutation identification by the reverse dot blot hybridization technique [RDB] and detection of XmnlGg polymorphism by RFLP. The frequency of positive heterozygote Xmnl gene polymorphism was 8.3%. Eighty-three percent of XmnIGy [+] patients were never transfused [p = 0.001] and had higher total hemoglobin compared to XmnlGy [p = 0.01]; while mean HbF was higher among XmnIGy patients compared to the other group but the difference was marginally insignificant [p = 0.06]. p-Thalassemia mutation TVS II-1 showed relatively higher Xmnl polymorphism frequency [50%] and followed by its frequency among 10 undefined P-thalassemia mutations which was 20%. The frequency of positive heterozygote Xmnl 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. I/ 6 none responder had positive heterozygote Xmnl gene polymorphism [p = 1.0]. 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
ABSTRACT
HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in [3-thalassemia patients and carriers remains controversial. We aimed to determine the prevalence of HFE gene mutations [C282Y and H63D] in [3-thalassemia patients and carriers and to investigate its effect on their serum ferritin levels. A total of 100 [3-thalassemia subjects; 75 patients and 25 carriers were screened for HFE gene mutations by PCR-RFLP. Serum ferritin measured by ELISA was evaluated in relation to HFE mutations. Twenty-eight [3-thalassemia patients [37.3%] were heterozygotes for H63D mutation [H/D], 8 [10.7%] were D/D and 39 [52%] were negative [H/H]. Among carriers, 4 [16%] were D/D and 21 [84%] were H/H homozygotes. C282Y mutant allele was not detected in any of the subjects. Serum ferritin levels were significantly higher in p-thalassemia patients heterozygotes or homozygotes for H63D mutation compared to those without mutation [p = 0.000]. Carriers homozygotes for H63D mutation showed significantly higher serum ferritin levels compared to those without mutation [p < 0.001]. Homozygosity for H63D mutation tends to be associated with higher ferritin levels in beta-thalassemia patients and carriers suggesting its modulating effect on iron load in these cases