Advances in immunosuppressive therapy allowed renal transplantation to become the treatment of choice for suitable candidates with (end stage renal disease) ESRD. The post-transplant therapeutic strategy is difficult due to narrow therapeutic indices for the currently used immunosuppressive drugs. Inter-individual differences in drug bioavailability are related to genetic and non genetic factors. The idea of targeted and personalized therapy is to achieve therapeutic success. The empirical dose has lost its value in the post-transplant therapy and an individualized dosage regimen must be established. Interindividual heterogeneity in expression of ABCB1 and CYP3A4 has been suspected to be one of the factors resulting in cyclosporine (CsA) pharmacokinetic variation. This study aimed to investigate the impact of inter-individual CYP3A4 rs4646437C>T and MDR1 G2677T/A polymorphisms on cyclosporine dose requirements among a sample of renal transplant Egyptian recipients. Fifty adult Egyptian patients on CsA were genotyped for CYP3A4 rs4646437C>T and MDR1 G2677T/A and correlated with CsA dose requirement and dose-adjusted CsA (C0) blood levels at 3, 6, and 9 months post transplantation. CYP3A4 rs4646437C>T influenced significantly cyclosporine kinetics, the T carriers requiring higher cyclosporine dose. Daily dose requirements were also significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation. Genotyping of both CYP3A4 and MDR1 SNPs may be helpful in providing pre-transplant pharmacogenetic information to individualize CsA dosing. Heterozygous CT genotype is the most frequent CYP3A4 rs4646437C>T genotype in the studied group of Egyptian population (48 %) followed by CC genotype and TT genotype. Daily dose requirements were significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation.

Background: Methotrexate is the most commonly used disease-modifying anti-rheumatic drug (DMARD) and it is considered the first-line treatment in the management of rheumatoid arthritis (RA). MTX treatment outcome regarding response to the drug and adverse effects in RA patients are not universal. Therefore, it would be beneficial if we could predict the response of patients to MTX before starting MTX treatment in order to determine the patient ' s drug-treatment plan. Objectives: The present study aimed to evaluate the impact of MTHFR A1298C SNP (rs1801131) on the clinical outcome of MTX treatment as regards treatment efficacy and toxicity in a cohort of Egyptian rheumatoid arthritis patients. Patients and methods: Fifty rheumatoid arthritis patients were included in the present study. Data about patient related variables such as age and sex, disease related variables such as disease duration as well as treatment related variables such as treatment duration, dose of MTX, its route of administration and concomitant use of other drugs (NSAIDs) were obtained. DAS28 was calculated to all patients to assess drug response. MTHFR A1298C polymorphism was investigated using real time 5 0 nuclease allelic discrimination assay. Results: Multivariate regression analysis for factors predicting MTX drug response showed that MTHFR A1298C SNP and MTX dose were the most significant independent predictors for MTX treatment response (p = .016, OR = 39.113, 95% C.I = 1.970-776.558, p = .003, OR = 1.667, C.I = 1.184-2.348, respectively). Considering clinicopathological variables; longer disease duration, positive anti-CCP, NSAIDs users, higher MTX doses and longer treatment durations were significantly associated with nonresponse to MTX. Regarding MTX drug toxicity, MTHFR 1298 CC genotype, MTX dose and concomitant use of NSAIDs were significantly associated with MTX drug toxicity (MC p = .003, p = .031, p = .029, respectively). Conclusion: Our study proved that MTHFR A1298C SNP can predict clinical outcome of MTX treatment as regards treatment efficacy and toxicity in Egyptian rheumatoid arthritis patients.

No abstract

Aim of the study: Ultrasound surveillance for hepatocellular carcinoma (HCC) among cirrhotic patients is the currently used modality but it is operator dependent. Combining a tumor marker with ultrasound may improve sensitivity for early HCC detection. Our aim was to assess the galectin-3 level among HCC and cirrhotic patients on top of chronic hepatitis C to evaluate its possible role as a tumor marker for HCC surveillance among cirrhotic patients. Material and methods: The study was conducted on 160 subjects. They were grouped as follows: group 1: 40 patients with HCC secondary to liver cirrhosis on top of chronic hepatitis C; group 2: 40 patients with cirrhosis secondary to chronic hepatitis C; group 3: 40 patients with chronic hepatitis C without advanced fibrosis; group 4: 40 healthy controls. Serum galectin-3 levels were determined in all subjects using ELISA. Results: Serum galectin-3 level was significantly higher in HCC patients than in those with chronic hepatitis C (p < 0.001). Also it was significantly higher among cirrhotic patients than in patients with chronic hepatitis C (p < 0.001). But on comparing HCC patients with cirrhotic patients, serum galectin-3 levels were not significantly different (p = 0.926). Conclusions: Galectin-3 levels cannot be used as an additional method for surveillance of HCC among cirrhotic patients.

Background Vitamin D (vit D) deficiency has recently been associated with risk of development of rheumatoid arthritis (RA). The aim of this research was to assess vitamin D receptor (VDR) gene expression in Egyptian patients with RA and its relation with the inflammatory state, disease activity, and functional disability. Results RA patients had significantly lower vit D level and VDR gene expression compared to controls (mean ± 17.0 ± 6.65, 20.73 ± 8.42 ng/ml, p < 0.05 and 3.29 ± 5.47, 14.22 ± 12.60, p < 0.001 respectively). Receiver operating characteristic (ROC) curve analysis for VDR gene expression in RA patients revealed (area under the curve 0.826, cutoff value for low VDR expression 1.05 ng/ml). Patients with low VDR expression had significantly higher ESR, CRP, double positive RF+ anti-CCP+, DAS28, and MHAQ (p < 0.001, p = 0.001, p < 0.05, p < 0.001, p < 0.001) respectively. Conclusion Vitamin D and VDR expression are significantly lower in RA patients than controls. Patients with low VDR gene expression had significantly higher disease activity and disability. This may suggest that apart from low vit D levels, low VDR expression is associated with inflammatory process and it has a potential role in RA pathogenesis and prognosis. Further multicenter studies are needed to confirm these findings.

Objective: The aim of this study was to measure serum zinc-α2-glycoprotein (ZAG) in pregnant Egyptian females with preeclampsia and eclampsia and to correlate its levels to biochemical measures of kidney function, lipid and glucose metabolism. Study Design: It was a retrospective study. Patients and Methods:This study measured ZAG levels by enzyme linked immunosorbent assay (ELISA) in pregnant females with preeclampsia (PE) (no. = 40) and eclampsia (no.=20) and were compared to healthy gestational age-matched subjects (no.=20). In addition, the association of ZAG with kidney function, lipid and glucose metabolism was studied. Results: Significant difference was detected on comparing the different groups regarding ZAG levels (p = 0.001). Furthermore, ZAG was positively correlated to systolic blood pressure, urinary protein, fasting insulin and HOMA-IR. After adjusting for other parameters,the association between ZAG and SBP, urinary protein, serum insulin and HOMA-IR remained significant by multivariate linear regression analysis. Conclusion: The study noted that maternal ZAG serum levels are significantly increased in PE.

Background Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility. Methods A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk. Results We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03–136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23–31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7–110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6–36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001). Conclusion AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP.

No abstract