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The present study aimed at evaluating the role of IL-1β −511 promoter and IL-1β +3953 exon 5 gene polymorphisms in the risk of developing rheumatoid arthritis (RA) and its correlation to disease activity in Egyptian patients. Thirty-two patients having RA as defined by American College of Rheumatology and 20 healthy control subjects were included. All were subjected to DNA analysis for IL-1β −511and IL-1β +3953 gene polymorphisms using PCR-RFLP technique with restriction enzymes AvaI and TaqI, respectively. No special pattern of association could be detected either between IL-1β −511 and +3953 gene polymorphisms and disease susceptibility or between the polymorphisms and the disease activity parameters represented by disease activity score 28 (DAS 28), ESR, and number of swollen and tender joints. Allele distribution failed as well to detect any association with either disease susceptibility or activity; however, a trend towards positive association involving IL-1β −511 C allele was observed ( P = 0.054). Our results suggest that IL-1β −511 and IL-1β +3953 gene polymorphisms do not influence the susceptibility to acquire RA in our population with no relation to disease activity. The complex role of the genetic factors in RA and the magnitude of the effects will require further thorough confirmations in other populations and on larger samples to acknowledge this issue. [ABSTRACT FROM AUTHOR]

Background: Warfarin is the most frequently prescribed oral anticoagulant worldwide. Due to its narrow therapeutic index and inter-patient variability in dose requirement, this drug has been considered an ideal target for personalised medicine. Several warfarin dosing algorithms have been proposed to tailor the warfarin dosage in the European, Asian and African-American populations. However, minimal interest was directed towards Middle East countries. The factors affecting warfarin dose requirement could be different in patients from different geographical and ethnic groups, limiting the value of published dosing algorithms. Objective: The first objective of this study was to examine the contribution of genetic and nongenetic factors on the variability of warfarin dose requirements in the Egyptian population using an easy, cost-effective and rapid analysis of vitamin K epoxide reductase complex subunit 1 ( VKORC1) and cytochrome P450 ( CYP) 2C9 single nucleotide polymorphism (SNP) genotyping of patients. A second objective was to develop and validate an algorithm for warfarin dose prediction that is tailored to Egyptian patients. Methods: Eighty-four patients, 41 males and 43 females, with a median (25th–75th percentiles) age of 39 (31–48) years were recruited in this study. Fifty patients whose international normalised ratio (INR) was in the range of 2–3 were allocated to a study cohort. SYBR Green-based multiplex allele-specific real-time PCR was used for genotyping of CYP2C9 (1075A>C) and VKORC1 (1173C>T) polymorphisms. Linear regression analysis, including the variables age, gender, CYP2C9 and VKORC1 SNP genotypes, was run to derive the best model for estimating the warfarin dose that achieves an INR of 2–3. The new warfarin dosing algorithm was examined in a second cohort of patients ( n = 34) to check its validity. The predicted dose requirements for a subgroup of our patients were calculated according to Gage and International Warfarin Pharmacogenetics Consortium (IWPC) algorithms available at http://www.warfarindosing.org. Results: In the study cohort, warfarin dose/week in VKORC1 TT subjects was statistically significantly lower than in VKORC1 CC/CT subjects ( p = 0.032), while there was no statistically significant difference in warfarin dose/week between CYP2C9*1*1 and *1*3 ( p = 0.925). A multivariate stepwise linear regression analysis revealed that age and VKORC1 had independent and significant contributions to the overall variability in warfarin dose with a p-value = 0.013 and 0.042, respectively. Maintenance dose (mg/week) = 65.226 − 0.422 × (age) − 9.474 × ( VKORC1). The estimated regression equation was able to account for 20.5 % of the overall variability in warfarin maintenance dose. A significant positive correlation, with sufficient strength, was observed between the predicted warfarin dose and the actual prescribed dose ( r = 0.453, p = 0.001). In the validation cohort, after application of the dosing algorithm, correlation between predicted and actual dose was statistically significant ( p = 0.023). The equation was particularly successful among patients with a dose ≥35 mg/week. The correlation coefficient between the actual and predicted doses for IWPC and Gage were 0.304 and 0.276, respectively. When compared with our algorithm ( r = 0.279), the difference was non-significant: p = 0.903 and 0.990, respectively. Conclusion: VKORC1 (1173C>T) contributes to the warfarin dose variability. Patients’ age and genetic variants of VKORC1 account for nearly 20.5 % of the variability in warfarin dose required to achieve an INR of 2–3. The success of a prediction equation based on these variables was proved in a different cohort: the predicted dose correlated significantly with the maintenance dose and the equation was more successful among patients with a dose ≥35 mg/week. The results of the warfarin algorithm we developed were comparable with those of the IWPC and Gage algorithms with the advantage of using one SNP ( VKORC1 1173C>T) only. This represents an economic advantage in our community. Replication of this study in a larger cohort of patients is necessary before translation of this knowledge into clinical guidelines for warfarin prescription. [ABSTRACT FROM AUTHOR]

Background: Egypt has a high prevalence of hepatitis C virus (HCV) infection. Limitations of the current HCV treatment in children are low rate of sustained virological response, significant side effects and high expenses, making prediction of treatment response crucial. Aim: This study aimed to investigate association of single nucleotide polymorphisms (SNPs) in interleukins (IL) 10 , 28 and 29 genes in predicting the response to therapy in HCV infected children. Methods: Sixty-six Egyptian children infected with HCV genotype 4, receiving pegylated interferon alpha 2b and ribavirin, were included. Genotyping of six SNPs in interleukin 10 , 28B and 29 gene as well as HCV genotype were analyzed by real-time polymerase chain reaction. Results: The CC genotype in IL28B; rs12979860 had 8.547 folds higher chance to develop sustained virological response than CT and TT genotypes ( P = 0.014). Genotype distribution of rs8099917 in IL28B gene ( TG and GG genotypes) was found to be 3.348 more likely not to respond to treatment than the TT genotype ( P = 0.018). In multivariate analysis, interleukin 28 gene single nucleotide polymorphisms rs 12979860 , interleukin 10 single nucleotide polymorphisms − 592A > C and basal viral load were independent variables that significantly improved prediction of response to HCV therapy. Conclusion: This association can be translated into clinical decision making for HCV treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms. Methods: VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls. Results: Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc<0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc<0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis. Conclusions: The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations. [Copyright &y& Elsevier]