ABSTRACT
OBJECTIVE: To evaluate the possible relationship between hydroxyurea (HU) response and some single-nucleotide polymorphism (SNP) in patients affected by ß-thalassemia intermedia. MATERIALS AND METHODS: In this cross-sectional study, 100 ß-thalassemia intermedia patients who were taking HU with a dose of 8 to 15 mg/kg body weight per day for a period of at least 6 months were randomly selected between February 2013 and October 2014 in southern Iran. HU response was defined based on decrease or cessation of the blood transfusion need and evaluation of Hb level. RESULTS: In univariate analysis, from all evaluated SNPs, only rs10837814 SNP of olfactory receptors (ORs) OR51B2 showed a significant association with HU response (P=0.038) and from laboratory characteristics, only nucleated red blood cells showed significant associations (116%±183%) in good responders versus (264%±286%) in poor responders (P=0.045). In multiple logistic regression, neither laboratory variables nor different SNPs, showed significant association with HU response. Three novel nucleotide variations (-665 [AâC], -1301 [TâG],-1199 delA) in OR51B2 gene were found in good responders. CONCLUSIONS: None of the evaluated SNPs in our study showed significant association with HU response. Further larger studies and evaluation of other genes are suggested.
Subject(s)
Hydroxyurea/administration & dosage , Polymorphism, Single Nucleotide , beta-Thalassemia/genetics , Adolescent , Adult , Blood Transfusion/statistics & numerical data , Cross-Sectional Studies , Female , Hemoglobins/analysis , Humans , Hydroxyurea/pharmacology , Iran , Logistic Models , Male , Receptors, Odorant/genetics , Treatment Outcome , Young Adult , beta-Thalassemia/drug therapyABSTRACT
BACKGROUND: Recent studies regarding the effect of hydroxyurea (HU) in thalassemia have revealed favorable effects on the reduction of ineffective erythropoiesis. OBJECTIVES: The aim of the current study was to evaluate whether or not HU can have an effect on the gallstone formation rate in patients with beta-thalassemia intermedia (BTI). PATIENTS AND METHODS: In this case control cross-sectional study, from a total of 250 transfusion-independent BTI patients, 51 patients who were taking HU, participated in the study. Patients were registered in the Thalassemia clinic of Shiraz University of Medical Sciences, Shiraz, which is a referral center located in southern Iran, during 2011-2012. Mean dose of HU consumption in the case group was 10 ± 2.5 mg/kg/day (range of 8-15 mg/kg/day), with a mean duration of consumption of 7.5 ± 3.8 years (range 1-14 years). In addition, 41 age- and sex-matched BTI patients who did not use HU were randomly selected as a control group. All patients underwent abdominal ultrasound by a radiologist for evaluation of gallstones. RESULTS: Mean age of the participants was 21.4 ± 6.5 years (10-40 years). There was no statistically significant difference regarding the frequency of cholelithiasis between the two groups of patients (P = 0.822). Our study showed significantly lower hemoglobin levels and a higher percentage of nucleated red blood cells in the HU group compared with the control group (P = 0.001 and P = 0.005, respectively). CONCLUSIONS: It seems that taking HU for long periods can reduce hemolysis and bone marrow suppression, and that decreases the rate of cholelithiasis. We believe that if these patients had not been treated with HU, we would probably have observed a significantly higher frequency of cholelithiasis, due to more hemolysis compared with patients not taking HU. Further studies with larger sample sizes are suggested.
