Yousri M. Hussein

Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: A case–control analysis

The aim of the study was to investigate whether polymorphisms in genes encoding Toll-like receptors (TLR2 and TLR4) may modify relative risk for development of asthma or allergic rhinitis. The results showed that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between asthmatic children or allergic rhinitis when compared to controls (p>0.05 for each) or even when compared further with IgE level. However, it was shown that the mutant allele of TLR2 or TLR4 polymorphisms were significantly associated with the moderate-severe group compared to the mild group in both atopic asthmatics and allergic rhinitis group (p>0.001 for each). In conclusion, our study demonstrates a lack of association of TLR2 and TLR4 polymorphisms with asthma and allergic rhinitis but suggests significant association between these genetic variants and the disease severity.

Association of tumor necrosis factor alpha and its receptor polymorphisms with rheumatoid arthritis in female patients

Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with altered expression of pro-inflammatory cytokines. We aim to elucidate the association between the -308G/A polymorphism of the TNF-α gene and 196M/R polymorphism in TNFRII gene and susceptibility and severity of RA. One hundred and seventy-two RA patients and one hundred and sixty controls were enrolled in the study. Polymorphisms (SNPs) at position -308 of TNF and -196 of TNFRII genes were determined using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). TNF AA genotype was more prevalent among the patients. GG genotype was significantly more likely to have erosive arthropathy. TNFRII RR genotype was more prevalent among the patients. Our findings suggest that the 308AA genotype of TNF-α and TNFRII 196M/R polymorphism are associated with RA susceptibility. While only the 308GG genotype of TNF-α is associated with RA severity.

Renin-angiotensin system genes polymorphism in Egyptians with premature coronary artery disease.

Genetics polymorphism of the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the RAS genes and premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late onset CAD and 119 controls were included in the study. Angiotensin converting enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT) genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86 respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides and LDL cholesterol were independent risk factors for the development of PCAD. We conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the susceptibility of an individual to have PCAD. The coexistence of CAD risk factors with these risky RAS genotypes may lead to the development of PCAD in Egyptian patients.

Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population.

BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population. MATERIALS AND METHODS One hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA). RESULTS Subjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters. CONCLUSION IL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.

Association between genes encoding components of the IL-10/IL-0 receptor pathway and asthma in children

BACKGROUND Asthma is a chronic inflammation of the airways associated with recurrent symptoms that range from mild to debilitating. Interleukin-10 (IL-10) is a cytokine that displays pleiotropic effects in asthma and allergy. OBJECTIVE To determine whether polymorphisms of IL-10/IL-10R pathway contribute to asthma susceptibility in Egyptian children. METHODS The IL-10 (-1082G/A), IL-10R1 (G330R), and signal transducer and activator of transcription 3 (STAT3) rs2293452 single-nucleotide polymorphism (SNP) were genotyped in 110 atopic children with asthma, 110 non-atopic children with asthma, and 110 healthy children. Serum IL-10 and immunoglobulin E (IgE) levels were determined by enzyme-linked immunosorbent assay. RESULTS A significant association was observed between the IL-10 polymorphism and asthma in both atopic (P = .03) and non-atopic asthma groups (P = .04). The genotype frequencies of IL-10R1 polymorphisms did not differ between all groups. We identified a significant association between STAT3 polymorphism and asthma susceptibility in atopic asthma (P < .001), whereas no such association was observed in the non-atopic asthma group (P = .9). No evidence of gene interactions was found. CONCLUSION Polymorphisms of IL-10 and STAT3 may be useful as a new DNA-based diagnostic biomarker for identifying high-risk children susceptible to asthma.

Association of interleukin-4 receptor gene polymorphisms with rheumatoid arthritis in Egyptian female patients

OBJECTIVES The imbalance between proinflammatory and anti-inflammatory cytokines is a feature of rheumatoid arthritis (RA). The role of interleukin-4 (IL-4) and its receptor in the pathogenesis of RA is conflicting. We aim to investigate the role of polymorphisms in the IL-4Rα gene in susceptibility and severity of RA. METHODS One hundred and seventy-two RA patients and 172 controls were enrolled in the study. Genotyping of IL-4Rα I50V (rs1805010) and IL-4Rα Q576R (rs1801275) was determined by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). RESULTS IL-4Rα I50V genotype was significantly more frequent in patients with RA than in controls (OR: 1.97, 95% CI: 1-3.7, P: 0.035). Subjects with IL-4Rα V50V genotype were significantly more likely to have erosive arthropathy (OR: 2.6, 95% CI: 1.1-6.1, P: 0.02). The frequencies of IL-4Rα Q576R genotype were significantly decreased in patients with erosive RA compared to patients with nonerosive RA (31.6% versus 48.2%, OR: 2.7, 95% CI: 1-7.7, P: 0.04). CONCLUSION IL-4Rα polymorphisms were associated with susceptibility to RA and may be helpful in early detection of erosive RA.

Interaction between TGF-β1 (869C/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis.

OBJECTIVES Rheumatoid arthritis (RA) is a chronic inflammatory disease. Transforming growth factor-β1 (TGF-β1) may be a promising candidate gene for susceptibility and severity in RA. We aimed to determine whether TGF-β1 polymorphism is associated with susceptibility to RA and progression of joint destruction, as well as to identify the interaction between TGF-β1 polymorphism and biochemical risk factor. METHODS A total of 160 RA patients and 168 healthy unrelated controls were tested for the TGF-β1 (869C/T) polymorphism using polymerase chain reaction. RESULTS The TGF-β1 T allele was associated with susceptibility to RA. Within the RA group, TGF-β1 T allele carriers had a significant increased risk to develop osteoporosis (OR=4.4, 95% CI=-2. 4-8.1, P<0.001), as well as more likely to develop bone erosion (OR=1.7, 95% CI=0. 99-2.7, P=0. 034). Better prediction was achieved when the TGF-β1 TT genotype was used in combination with either elevated, rheumatoid factor (RF) or C-reactive protein (CRP) (OR=6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR=3.3, 9.8, P=0.017, 0.001 respectively). CONCLUSION Our results suggest that TGF-β1 TT genotype may determine the development of osteoporosis and bone erosion in RA. Also, our results points to a synergism between TGF-β1 TT genotype and elevated serum RF or elevated CRP that lead to the development of osteoporosis and bone erosion in patients with rheumatoid arthritis.

Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children.

OBJECTIVE To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. METHODS We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. RESULTS There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, <0.001 respectively), whereas no such association was observed in non-AD group (p=0.52, 0.99 respectively). A significant association between STAT6 polymorphisms and both types of dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. CONCLUSION In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individuals susceptibility to AD.

MAGE-3 and MAGE-4 genes as possible markers for early detection of metastases in hepatitis C virus Egyptian patients complicated by hepatocellular carcinoma

The dissemination of hepatocellular carcinoma (HCC) cells into the circulation plays a critical role in post-operative recurrence and metastasis. Early detection of metastatic tumor cells is critical to identify HCC patients at high risk of relapse. MAGE-3 and -4 genes were evaluated by reverse transcription polymerase chain reaction for the possibility of using them as new markers for early detection of metastases in 160 chronic HCV Egyptian patients, 115 of them were complicated with HCC. The expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with metastatic HCC were 36 and 52%, respectively. While the expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with localized HCC were 12.5 and 15%, respectively. Moreover, at least one type of mRNA was found in the peripheral blood of 68% of the metastatic HCC patients and in 20% of the localized HCC patients. While neither the controls nor the cirrhotic patients show expression of MAGE-4 mRNA in their peripheral blood. MAGE-3 and MAGE-4 may be a promising diagnostic tool for monitoring the prognosis of HCC patients and early detection of occult hematogenous metastasis of HCC.

Association of serum cytokines levels, interleukin 10 -1082G/A and interferon-γ +874T/A polymorphisms with atopic asthma children from Saudi Arabia.

The aim of this study was to clarify the role of IL-4, IL-10, IL-13 and interferon (IFN) -γ levels in atopic asthma patients by studying the relation between their serum levels and severity of the disease. The effect of IL-10 -1082G/A and IFN-γ +874T/A SNPs was also studied. The study included 200 atopic children with asthma and 50 age- and gender matched healthy children as controls. The levels of both IL-4 and IL-13 were significantly (p<0.001) higher, while IFN-γ was significantly (p<0.001) lower in patients compared to that of the controls. There was a significant effect of gene polymorphisms of IL-10 (p<0.05) and IFN-γ (p<0.001) in occurrence of atopic asthma and increased IgE level. Polymorphism of IFN-γ gene had an effect on the serum level of IFN-γ. In conclusion, IFN-γ gene polymorphism at position +874 and IL-10 gene polymorphism at position -1082A/G are genetic determinants which contribute to susceptibility to atopic asthma in children from Saudi Arabia.