ABSTRACT
BACKGROUND AND STUDY AIMS: The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity. PATIENTS AND METHODS: This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed. RESULTS: Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002). CONCLUSIONS: MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.
ABSTRACT
Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.