Hoda A. Hagrass

Cytokines genes polymorphisms in chronic hepatitis C: impact on susceptibility to infection and response to therapy.

BACKGROUND Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection, the production of abnormal cytokine levels appears to contribute in the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes polymorphisms located within the coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the study was to evaluate the association of of IL28B rs12979860, TGF-β1-509, TNF-α 308, and IL-10-1082 polymorphisms with the susceptibility to hepatitis C virus genotype 4 infection and response to pegylated interferon-α and ribavirin therapy. METHODS IL28B, TGF-β1 and TNF-α genes polymorphisms were genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay while IL-10 gene polymorphism was detected by sequence specific primer-PCR in 220 healthy individuals and 440 hepatitis C infected patients (220 sustained virological response and 220 non-responder to combination therapy). RESULTS IL28 B CT and TT, TGF-β1 CT and TT and TNF-α AG and AA genotypes were significantly associated with susceptibility to hepatitis C infection and response to therapy. While no association was found between IL-10 gene polymorphism and susceptibility to HCV infection and response to treatment. CONCLUSIONS These results suggested that inheritance of IL28B CT and TT, TGF-β1 CT and TT and TNF-α AG and AA genotypes which appear to affect the cytokine production may be associated with susceptibility to HCV infection and resistance to combined antiviral therapy.

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

BACKGROUND Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM. MATERIALS AND METHODS One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA. RESULT Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P=<0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR=2.3, 95% CI=1.3-4.2, P=0.005; OR=2.2, 95% CI=1.1-4.7, P=0.04; OR=1.8, 95% CI=1.03-3.04, P=0.04; OR=4.03, 95% CI=1.2-13.1, P=0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not. CONCLUSION Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.

Baseline serum level of matrix metalloproteinase‐3 as a biomarker of progressive joint damage in rheumatoid arthritis patients

Matrix metalloproteinase‐3 (MMP‐3) plays a pivotal role in the destruction of bone and degradation of cartilage components in rheumatoid arthritis (RA). We aimed in this study to analyze the relation between baseline levels of MMP‐3 and the progression of joint damage in RA.

Increased risk of premature coronary artery disease in Egyptians with ABCA1 (R219K), CETP (TaqIB), and LCAT (4886C/T) genes polymorphism

BACKGROUND Epidemiological studies have shown a strong inverse relationship between high-density lipoprotein (HDL) cholesterol (HDLc) levels and coronary artery disease (CAD), and a low concentration of plasma HDLc is considered an independent risk factor for premature atherosclerosis. Mutations in ATP-binding cassette A1 transporter (ABCA1), cholesteryl ester transfer protein (CETP), and lecithin: cholesterol acyltransferase (LCAT) reduce HDLc in humans. OBJECTIVE To date, no study had tested the association between these polymorphisms and premature CAD (PCAD) in the Egyptian population. Here we searched for ABCA1 (rs2230806), CETP (rs708272), and LCAT (rs5923) mutations in the Egyptian population and investigated the possible association between these gene polymorphisms and PCAD. We aimed to investigate the association between ABCA1, CETP, and LCAT gene polymorphisms and PCAD in Egyptians. METHODS A total of 235 Egyptians-116 with documented PCAD (PCAD group) and 119 controls-were enrolled in the study. RESULTS Mutation carriers with low HDLc had an elevated risk of PCAD (odds ratio [OR] = 11.38 for ABCA1 mutation carriers, P = .000; OR = 5.41 for CETP mutation carriers, P = .000; OR = 5.92 for LCAT mutation carriers, P = .000). Moreover, mutations in ABCA1, CETP, and LCAT were significantly associated with hyperlipidemia in this study. CONCLUSION These observations show that the R allele of ABCA1, the B1 allele of CETP, and the T allele LCAT genes are associated with PCAD in Egyptians. They have more considerable effect on patients with low HDLc.

Association of FcγRIIB and FcγRIIA R131H gene polymorphisms with renal involvement in Egyptian systemic lupus erythematosus patients

Identification of the genetic basis of systemic lupus erythematosus (SLE) may contribute to the discovery of effective drugs before renal involvement. Our aim of this study was to estimate the association between Fc gamma receptor (FcγR) polymorphisms and SLE and renal involvement in Egyptian patients. FcγRIIB and FcγRIIA R131H gene polymorphisms were genotyped in 180 Egyptian adults. Genotyping for FcγRIIA R131H was performed using allele-specific PCR and FcγRIIB-Ile232 Thr polymorphism was genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP). The study showed that the homozygous genotype (Thr/Thr) of FcγRIIB significantly increased in all SLE patients (90 patients) and in SLE patients complicated with nephritis (61 patients). The Thr allele was significantly associated with an increased risk of the disease in all the patients and in patients complicated with nephritis. Our study demonstrated an association of FcγRIIB polymorphisms with SLE and lupus nephritis and a lack of association of FcγRIIA polymorphisms with SLE in the Egyptian patients.

Estrogen receptor alpha (ERα) promoter methylation status in tumor and serum DNA in Egyptian breast cancer patients

BACKGROUND Status of DNA methylation is one of the most common molecular alterations in human neoplasia. Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated the aberrant DNA methylation status of estrogen receptor alpha (ERα) in patient pretherapeutic sera and tissue. MATERIALS AND METHODS In this case control study the patient series consisted of 120 sporadic primary breast cancer cases and 100 patients with benign breast lesion. ER3, ER4, and ER5 primers were used for methylation-specific polymerase chain reaction (MSP) to analyze the CpG methylation of promoter region of ERα gene. Correlation between ER3, ER4, and ER5 methylation and clinicopathological characteristics of the patients was investigated. RESULT The methylation status of ER3, ER4 and ER5 was 65%, 26.7% and 61.7% in tissue respectively and 57.5%, 21.7% and 55.8% in serum respectively. The concordance between tumor and serum DNA methylation was 80%, 72% and 92% for ER3, ER4 and ER5 respectively. CONCLUSIONS This study demonstrated the potential utility of serum DNA methylation of ERα gene promoter as a non-invasive diagnostic and/or prognostic marker in patients with breast cancer.

The Role of CTLA-4 Exon-1 49 A/G Polymorphism and Soluble CTLA-4 Protein Level in Egyptian Patients with Behçet's Disease

This study analyzed the association of the A/G SNP at position +49 of exon-1 in the CTLA-4 gene to the susceptibility and clinical manifestations of Behcets disease (BD). It was performed on 60 Egyptian BD patients and 95 age- and sex-matched healthy controls. The genotypes for the +49 A/G polymorphism of the CTLA-4 gene were determined by PCR-RFLP, while the serum level of CTLA-4 protein was measured by ELISA. CTLA-4 +49 A allele (P < 0.001, OR = 3.084, and CI (95%) = 1.90–4.99) and A/A genotype (P < 0.001, OR = 6.643, and CI (95%) = 2.58–17.10) frequency distribution was significantly more increased in patients than in the controls, with no significant differences between males and females with regard to the genotype or allele frequency distribution. A/A genotype was associated with a more reduced expression of sCTLA-4 protein in patients than in the controls (1.76 ± 0.19 versus 1.91 ± 0.30, resp; P < 0.0007). In addition, it is associated with the occurrence of ocular and vasculitic manifestations of BD in the patient group. The CTLA-4 gene could be considered as a susceptibility and a disease-modifying gene to BD in Egyptian population that needs further confirmatory studies on larger cohorts.

Superantigen Gene Profile of Staphylococcus aureus Colonizing Egyptian Pediatric Patients with Atopic Dermatitis: Relationship to Disease Severity and Multi-Drug Resistance

Background: Eczematous skin of atopic dermatitis (AD) is highly susceptible to infection and colonization by Staphylococcus aureus and the superantigen toxins can worsen the condition. Objectives: To assess the colonization of Egyptian pediatric AD patients with S. aureus and to characterize the superantigen gene profile of isolates in relation to severity and to presence of multiple drug resistant (MDR) strains. Methodology: The study included 53 AD pediatric patients and 45 controls. Severity of AD was assessed by scoring atopic dermatitis (SCORAD) index. Swabs were collected to isolate S. aureus. Isolates were subjected to multiplex PCR reactions for detection of six superantigen genes and to antimicrobial susceptibility tests by disc diffusion method. Results: Colonization with S. aureus was significantly higher (P < 0.0001) in AD children compared to controls and was significantly associated (P= 0.001) with severity. Superantigen genes were detected in 30.1% of isolates. The most prevalent genes were sea (64.5%), seb (32.3%), sec (6.5%) and tsst-1 (3.2%). Multidrug resistance was found in 63.1% of strains. Severity of AD was significantly higher with strains harboring superantigen genes (P=0.04) and with MDR strains (P=0.0002). Among methicillin resistant S. aureus (MRSA), seb was the most prevalent superantigen gene (37.5%), while sea was most prevalent in methicillin-susceptible S. aureus (MSSA) (20%), MDR (23.1%) and non MDR isolates (13.2%).Conclusion: Superantigen genes and multidrug resistance are common in S. aureus colonizing AD patients and are associated with severity. More attention should be paid at performing antimicrobial susceptibility testing before antibiotic therapy.