Hemophilia A (HA) is the most common severe bleeding disorder in humans, affecting one in 5,000 male births. In severe HA, intron 22 inversion of F8 is the most prevalent mutation, accounting for 40-50% of all mutations; however, little is known about the disease-causing mutations among Egyptian hemophiliacs. We aimed at genotyping all possible known DNA rearrangements of intron 22 of F8 in Egyptian HA patients. Peripheral blood samples were collected from 30 Egyptian HA patients (13 severe, ten moderate, and seven mild cases). Genotyping of F8 intron 22 rearrangements was performed by inverse-shifting PCR (IS-PCR). Our study revealed that seven patients (23.3%) had inversion 22, three patients (10%) had deletion 22, and 20 patients (66.7%) carried the wild-type allele. No intron 22 duplication was detected. The relative proportion of inversion 22-type 1 to inversion 22-type 2 was 85.7% and 14.3%, respectively, whereas the relative proportion of deletion 22-type 1 to deletion 22-type 2 was 33.3% and 66.7%, respectively. A statistically highly significant relation was found between disease severity and F8 intron 22 rearrangements (p = 0.008). Among severe cases, 46.1% had inversion 22, 23.1% had deletion 22, and 30.8% carried the wild-type allele. We conclude that F8 intron 22 inversion/deletion is responsible for about one third of disease-causing mutations among Egyptian hemophiliacs and for nearly 70% in severe cases. In addition, F8 intron 22 inversion/deletion by IS-PCR has proven to be a rapid and robust technique and might be the recommended tool for genetic analysis of HA patients specially with severe cases in developing countries.

Abstract. Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic.

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Cytochrome P450 3A4 (CYP3A4) is the most plentiful cytochrome P450 in adult human liver and small intestine and is responsible for detoxification of more than 50% of drugs in addition to the metabolic deactivation and metabolism of many carcinogens. Polymorphism of CYP3A4-A-290G considered the only allele that appears to stimulate CYP3A4 expression and has been associated with a number of clinical phenotypes, including prostate cancer, breast cancer, leukemia and the early onset of puberty. In this study, we analyzed the presence of CYP3A4-A-290G polymorphism in 77 newly diagnosed AML cases and 72 healthy control using PCR/RFLP aiming to show CYP3A4-A-290G polymorphism pattern in acute myeloid leukemia patients, and its role in disease severity and progression. A highly statistically significant difference was found between the control and AML groups as regards the heterozygous genotype (p-value = 0.002) and increases the risk of AML 11.4-fold. Also there was a highly significant difference between the control and AML patients regarding variant allele (G in AG and GG genotypes) (p-value 0.001) and increases the risk of AML 19-fold. No statistically significant association found between the CYP3A4-A-290G polymorphism and different clinical or laboratory parameters as well as an initial response to treatment, overall survival and the disease free survival. We concluded that CYP3A4-A-290G polymorphism is a genotypic factor that increases the CYP3A4 enzymatic activity and increases the risk of AML by 18.9-fold.

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