Effect alpha globlin gene deletion and gamma globin gene -158 [C/T] polymorphism in beta-thalassemic patients

The beta-thalassemias [beta- thalassemias] are among the most common autosomal recessive disorders. They have a remarkably high frequency in the Mediterranean region and represent one of the most common genetic diseases in Egypt. In this study, the spectrum of beta-thalassemia mutations and genotype-to-phenotype correlations were defined in 32 beta- thalassemic patients [beta- thlassemias major and intermedia] with varying disease severity in two cities of the Suez Canal region. Ten different mutations were identified and the most frequent ones were: IVSI-6 [T-C] [37.5%], IVSI-110 [G-A] [34.4%] and both IVSI-1 [G-A], IVSII-745 [C-G] and -102 [C-G] [12.5% each]. There was a wide spectrum of phenotypic severity in all patients. We studied the Xmnl polymorphism [C/T] in gamma- globin gene position -158 of beta- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a modulating factor was not evident in our patients. In conclusion, we have been unable to find a molecular basis for the benign clinical course in all our patients. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition

Enhanced apoptosis of peripheral blood mononuclear cells from chronic hcv patients is associated with reduced caspase 3 activity

Background: Infection with hepatitis C virus [HCV] is a major cause of chronic liver disease throughout the world. Down-regulation of the immune response plays a major role in HCV persistence. Recent investigation suggest that apoptosis of peripheral blood mononuclear cells [PBMCs] contributes to such down-regulation

Objective: The current study investigates apoptotic changes in PBMCs and their relation to caspase-3 and -8 activities in patients with chronic HCV infection

Methods: Apoptosis were investigated by measuring annexin-V binding using flowcytometry and DNA fragmentation using agarose gel electrophoresis, and caspases-3 and -8 specific activities were also measured in 43 chronic HCV patients and 10 normal control subjects

Results: A significantly higher percent of annexin-V positive PBMCs was found in chronic HCV patients than controls [p<0.0001]. DNA fragmentation was detected in PBMCs from 20/43 patients [46.5%] but not from controls. There was no statistically significant difference between HCV-PCR positive and negative patients as regards the degree of PBMCs apoptosis. Caspase-3 activity was significantly lower in patients than controls [p=0.001], was significantly lower in HCV-PCR positive than controls [p=0.001] and was significantly higher in patients with PBMCs DNA fragmentation [p=0.005]. On the other hand, caspase-8 activity was comparable in both patients and control groups. However, patients with PBMCs DNA fragmentation showed statistically significant higher activity than those without [p=0.023]. There was a statistically significant direct correlation between caspase-3 and caspase-8 activities in the patients groups [r=0.56,p<0.0001]

Conclusion: Chronic HCV infection is associated with PBMCs apoptosis irrespective of the presence of viremia. However, this apoptosis is independent on activation of either caspase-3 or caspase-8