Multi-omics analysis of fecal samples in colorectal cancer Egyptians patients: a pilot study.

BACKGROUND: Colorectal cancer (CRC) is a public health concern and the second most common disease worldwide. This is due to genetic coding and is influenced by environmental aspects, in which the gut microbiota plays a significant role. The purpose of this study was to compare the microbiota makeup of CRC patients with that of healthy control and to identify upregulated and downregulated proteins and metabolites in CRC patients. Using a next-generation sequencing approach, fecal samples of five females (4 CRC patients and one healthy control) were analyzed by BGI DNBSEQ-T7, Hong Kong, China. Furthermore, proteomics and metabolomics analysis were performed using LC-MS/MS technique. RESULTS: Dysbiosis of gut microbiota has been observed in patients with CRC, with an increase in microbiota diversity at all taxonomic levels relative to healthy control. Where, at the functional level the bacterial species participate in many different pathways among them de novo nucleotide synthesis and amino acids pathways were aberrantly upregulated in CRC patients. Proteomics and metabolomics profiles of CRC patients showed different proteins and metabolites, a total of 360 and 158 proteins and metabolites, respectively were highly expressed compared to healthy control with fold change ≥ 1.2. Among the highly expressed proteins were transketolase, sushi domain-containing protein, sulfide quinone oxidoreductase protein, AAA family ATPase protein, carbonic anhydrase, IgG Fc-binding protein, nucleoside diphosphate kinase protein, arylsulfatase, alkaline phosphatase protein, phosphoglycerate kinase, protein kinase domain-containing protein, non-specific serine/threonine protein kinase, Acyl-CoA synthetase and EF-hand domain-containing protein. Some of the differential metabolites, Taurine, Taurocholic acid, 7-ketodeoxycholic acid, Glycochenodeoxycholic acid, Glycocholic acid, and Taurochenodeoxycholic acid that belong to bile acids metabolites. CONCLUSIONS: Some bacterial species, proteins, and metabolites could be used as diagnostic biomarkers for CRC. Our study paves an insight into using multi-omics technology to address the relationship between gut microbiota and CRC.

Association of endothelial nitric oxide synthase (Glu298Asp) gene polymorphism with radial artery spasm during cardiac catheterization in Egyptians.

BACKGROUND: Nitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization. METHODS AND RESULTS: 200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm. CONCLUSION: The eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.

Effect of N-Acetylcysteine on initial Carious Enamel Lesions in primary teeth: an In-vitro study.

BACKGROUND: Dental caries initiates with non-cavitated enamel lesions as the first stage. The cariogenic potential of N-Acetylcysteine (NAC) may be due to its usage frequency and form. This study aimed to evaluate the impact of exposure time of NAC on initial enamel caries-like lesions in primary teeth by assessing the morphological alteration using a scanning electron microscope (SEM) and mineral content using energy dispersive x-ray spectroscopy (EDX). METHODS: Forty primary incisor teeth were randomly divided into 4 groups S, S1, S2, and S3 (10 specimens/group). Teeth crowns were cut from their roots and inserted into an acrylic mold with its buccal surface directed upward. Centrally isolated enamel window (2 × 2 mm) on the tooth was done. Ten specimens were selected to evaluate normal enamel while the remaining thirty specimens were immersed in demineralizing solution for 96 h to produce enamel caries-like lesions. PH cycling was performed by immersing each tooth sample in 20 mL of demineralizing solution for 3 h then, preserved for the remaining day hours in 10 ml of artificial saliva interspersed with treatments applications with 10 ml NAC for 10 min twice a day for one- or three-months different treatment modalities. Thermocycling was done for all specimens then they were subjected to SEM and EDX analysis. ANOVA and Bonferroni post hoc tests were utilized in data analysis. RESULTS: In teeth treated by NAC for 3 months (group-S3), SEM images showed severe loss of enamel architecture with large NAC deposits detected. A meaningful difference was observed among different groups concerning calcium, phosphorus, fluoride, ca/P ratio, carbon, nitrogen, and oxygen contents (P < 0.05). CONCLUSION: NAC had a detrimental impact on enamel caries-like lesions in human primary teeth.

Associations between mental health problems and risky oral and sexual behaviour in adolescents in a sub-urban community in Southwest Nigeria.

BACKGROUND: This study determined the association between mental health and risky oral health and sexual health behaviours. METHODS: A household cross-sectional survey was conducted in Ile-Ife, Nigeria between December 2019 and January 2020. Data were collected from 10 to 19-year-old on the sociodemographic profile (age, sex at birth and socioeconomic status); mental health problems (psychological distress, depressive symptoms and suicidal ideation); and mental (smoking habit, consumption of alcohol, use of psychoactive substances), sexual (history of vaginal or anal sexual intercourse; transactional sex, multiple sex partners, use of condom at last sexual intercourse) and oral (frequency of daily tooth brushing, daily frequency of consumption of refined carbohydrate in-between-meals, frequency of use of dental floss, history of dental service utilization in the last 12 months and dental anxiety) health risk factors. Binary logistic regression analysis was conducted to determine the association between risky oral (neglecting to brush twice daily and frequent consumption of refined carbohydrates in-between-meals), and sexual (neglecting to use condoms during the last sex act and having multiple sex partners) health behaviours as outcome variables, and mental health status as the explanatory variables. An ordinal logistic regression model was also developed where the outcome variable was the number of risky health behaviours. The models were adjusted for the socio-demographic variables and history of dental service utilisation in the last 12 months of the survey. RESULTS: High psychological distress was significantly associated with lower odds of frequent consumption of refined carbohydrates in-between-meals (AOR = 0.32; 95%CI 0.23, 0.47), and having multiple sex partners (AOR = 0.10; 95%CI 0.02, 0.57); but higher odds of having a higher number of risky behaviours (AOR = 3.04; 95%CI 2.13, 4.33). Having depressive symptoms was significantly associated with higher odds of neglecting to use condom at the last sexual intercourse (AOR = 7.20; 95%CI 1.94, 26.76) and having multiple partners (AOR = 95.43; 95%CI 24.55, 370.90). Suicidal ideation was significantly associated with lower odds of neglecting to use condom at the last sexual intercourse (AOR = 0.00; 95%CI 0.00, 0.00) and having multiple sex partners (AOR = 0.00; 95%CI 0.00, 0.00). CONCLUSION: The associations between psychological distress and oral and sexual health risk behaviours in adolescents seem complex and need to be studied further.

Visual disability among patients attending glaucoma clinic in a tertiary hospital.

PURPOSE: To report visual impairment and blindness among the patients attending a glaucoma clinic in a tertiary university hospital and highlight the possible risk factors that could be addressed later. METHODS: A retrospective analysis of the medical records of the patients attending the glaucoma clinic in Ain Shams University Hospitals over a period of one year was conducted. Visual impairment classification was done according to the International Classification of Diseases and Related Health Problems (ICD-11) based on the best-corrected visual acuity in the better-seeing eye. Data including diagnosis, history of previous surgery, and duration of glaucoma were extracted and analyzed. RESULTS: The medical records of the first visit of 118 patients (58 males and 60 females) were included in this study. Secondary glaucoma was the most common type presented (38 patients, 32.2%), followed by primary open-angle glaucoma (35 patients, 29.6%). Sixty-seven patients (56.7%) were considered visually impaired, while seven patients (5.9%) were considered blind. Forty-one patients (34.7%) were considered mono-ocular blind. CONCLUSION: There is a high incidence of visual impairment and blindness among glaucoma patients presented to the glaucoma clinic in the  tertiary hospital. A further nation-wide study and possibly, an early surveillance program for glaucoma are needed.

Development and preliminary validation of the Adolescent Psoriasis Quality of Life instrument: a disease-specific measure of quality of life in adolescents with psoriasis.

BACKGROUND: No age-appropriate and disease-specific instrument currently exists to measure health-related quality of life in adolescents with psoriasis (patients aged 12-17 years). OBJECTIVES: To develop and provide preliminary validation of the Adolescent Psoriasis Quality of Life instrument. METHODS: Qualitative interviews with adolescents with psoriasis, parents of adolescents with psoriasis, and healthcare professionals informed the development of an initial item pool for the instrument, which was subsequently refined through cognitive interviews. Finally, data from an independent sample of adolescents with psoriasis (n = 50) were used for item reduction, scale construction and initial validation, using a combination of techniques from classical test theory and Rasch modelling. RESULTS: Rich qualitative data concerning health-related quality of life in adolescents with psoriasis (from 18 adolescents, 14 parents and four healthcare professionals), combined with cognitive interview testing (n = 12), resulted in a 41-item draft version. Item reduction led to the final version, a 17-item instrument consisting of two subscales showing good fit to their respective Rasch models: psychosocial impact (12 items) and the impact of physical symptoms and treatment (five items). All a priori stated hypotheses regarding construct validity were supported. Both subscales and the total scale showed acceptable test-retest reliabilities (intraclass correlations 0·97, 0·89 and 0·96) and internal consistencies (Cronbach's α 0·94, 0·81 and 0·95). CONCLUSIONS: The preliminary form of the Adolescent Psoriasis Quality of Life instrument shows promising psychometric properties. It can be used in daily clinical practice and research to support a patient-centred approach and inform treatment planning. What's already known about this topic? Health-related quality of life (HRQoL) instruments should be targeted towards narrowly defined age groups, as life contexts of children, adolescents and adults may differ substantially. Dermatology-specific instruments have been used to measure HRQoL in adolescents with psoriasis, but it is not known whether these instruments accurately capture all relevant HRQoL aspects in adolescent psoriasis. Age-appropriate and psoriasis-specific instruments may be more sensitive for HRQoL issues experienced by this unique group. What does this study add? The Adolescent Psoriasis Quality of Life instrument represents the first age-appropriate and disease-specific instrument for measuring HRQoL in adolescents (12-17 years old) with psoriasis. It is intended for use in daily clinical practice to support dermatologists and other healthcare professionals in providing optimal care for adolescents with psoriasis.

DNA Gyrase and Topoisomerase IV Mutations and their effect on Quinolones Resistant Proteus mirabilis among UTIs Patients.

OBJECTIVE: This study aimed to highlight the importance of mutations within Proteus mirabilis genome that are related to fluoroquinolone resistance. METHODS: This is a cross sectional study performed in different teaching hospitals in Khartoum State from June 2016 to May 2017. A total of (120) P mirabilis isolates from patients with symptoms of UTIs attending different hospitals in Khartoum State were examined. First, modified Kurby Bauer method was performed for phenotypical detection of resistant isolates. Then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing were applied for detection of mutations in GyrA, GyrB, ParC and ParE genes of isolates. RESULTS: P. mirabilis showed 30% resistance to ciprofloxacin. All samples revealed mutation at (serine 83) of GyrA and (serine 84) of ParC by Hinf1 restriction endonuclease digestion. Sequencing was performed for 12 samples. For each gene, two resistant and one susceptible strains were randomly selected. The mutations associated with ciprofloxacin resistant P. mirabilis were as follows; (1/3) GyrA (Ser 83 to Ile) and (2/3) ParC (Ser 81 to Ile). Also it revealed silent mutations at codons of GyrB 474 leucine (3/3), 585 valine (2/3), 612 histidine (1/3) and 639 asparagine (1/3) and ParE 469 isoleucine (2/3), 531 aspartic (2/3) and 533 glycine (1/3). CONCLUSIONS: Ciprofloxacin resistance in P. mirabilis could be monitored through detection of mutations within DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE).

Genetic and epigenetic modifications of adiponectin gene: Potential association with breast cancer risk.

BACKGROUND: Adipokines produced by adipose tissue are directly linked to obesity and may contribute to the pathogenesis of cancer. We hypothesized that genetic and epigenetic modifications in the adiponectin (ADIPOQ) gene and their impact on serum ADIPOQ levels may participate in increasing breast cancer (BC) risk. The present study aimed to investigate ADIPOQ +45 T/G gene polymorphism, methylation status at CpG sites -74 nucleotides (nt) and -283 nt of the ADIPOQ gene, and ADIPOQ serum levels in BC obese women. METHODS: Serum ADIPOQ was measured by an enzyme-linked immunosorbent assay. ADIPOQ +45 T/G gene polymorphism and ADIPOQ promoter methylation status were determined using a polymerase chain reaction (PCR) and a methylation-specific PCR, respectively, in 120 obese women with BC and 120 age-matched controls. RESULTS: ADIPOQ +45 GG genotype carriers had a significant increased risk of developing BC (odds ratio = 6.2, 95% confidence interval = 1.3-29.6, p = 0.02). ADIPOQ gene methylation at site -74 nt resulted in a 1.7-fold increased BC risk. Methylation at site -283 nt resulted in a 1.9-fold increased BC risk. Moreover serum levels of ADIPOQ were significantly decreased in BC patients and down-regulated in the presence of methylation in both examined sites. By contrast, no association between ADIPOQ gene polymorphism and serum ADIPOQ level was detected. Using both methylated sites in one panel detected cancer breast with 76.67% sensitivity and 62.18% accuracy. CONCLUSIONS: ADIPOQ +45 T/G polymorphism and ADIPOQ promoter methylation were found to be associated with BC risk in obese Egyptian women.

Health-related quality of life in adolescents with psoriasis: an interview-based study.

BACKGROUND: Psoriasis is a common skin disease affecting the physical, psychological and social well-being of patients and their families. Most research so far has been limited to adults, and little is known about the qualitative experiences of young people with psoriasis. OBJECTIVES: To provide an in-depth understanding of the impact of psoriasis on adolescents' health-related quality of life (HRQoL). METHODS: Patients and their parents were recruited from a dermatology outpatient clinic, the Danish National Birth Cohort and the Danish Psoriasis Association. Thirty-six semistructured interviews were conducted with adolescents with psoriasis aged 12-17 years (n = 18), their parents (n = 14) and health professionals working with psoriasis (n = 4). Interviews were digitally recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS: The participants reported psoriasis-related HRQoL challenges within six main themes: physical symptoms, feeling different, psoriasis-related worry about the future, increased attention, attempts to conceal skin, and treatment-related frustrations and worry. Taken together, a broad range of the reported difficulties appeared to arise from appearance-related concerns. The impact of psoriasis and its treatment on the adolescents' daily lives varied considerably. CONCLUSIONS: This first in-depth, qualitative study of HRQoL in adolescents with psoriasis provides a conceptual framework for understanding the impact of psoriasis and its treatment on the physical, psychological and social aspects of their daily lives.

Cyclooxygenase 2 (rs2745557) Polymorphism and the Susceptibility to Benign Prostate Hyperplasia and Prostate Cancer in Egyptians.

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression, and metastasis. We aimed to evaluate the association between COX-2 (rs2745557) polymorphism and prostate cancer (PCa), benign prostate hyperplasia (BPH) risk. We also assessed the influence of other risk factors such as obesity, smoking, diabetes in modulating the risk of PCa in Egyptian men. COX-2 (rs2745557) was genotyped in 112 PC patients, 111 BPH and 120 subjects as a control group. COX-2 and PSA levels were measured by ELISA. We found that GG genotype was associated with a 17-fold increased risk for PCa and 20-fold increased the risk for BPH more than AA genotype. Also, G allele carriers of COX-2 were associated with metastatic cancer (OR = 1.3, P < 0.05) and disease aggressiveness (OR = 3.5, P < 0.001). The coexistence of obesity, smoking, or diabetes with GG genotype may lead to increasing the risk of developing BPH (OR = 3.3, 4, and 2.7, respectively) and of developing PCa (OR = 2.9, 4.9, and 3.2, respectively). Our results showed evidence suggesting the involvement of the COX-2 (rs2745557) polymorphism and its protein in PCa or BPH initiation and progression. Also, the coexistence of COX-2 (rs2745557) and obesity, smoking, or diabetes may lead to the development of PCa or BPH.

Anti-oxidative and anti-apoptotic roles of spermatogonial stem cells in reversing cisplatin-induced testicular toxicity.

BACKGROUND AIMS: Because of reproductive toxic effects of chemotherapy, researchers have taken some techniques to preserve fertility potential. The present study was designed to point out the potential role of spermatogonial stem cell (SSC) therapy in reversing cisplatin (CP)-induced testicular toxicity and restore the spermatogenesis. METHODS: Sixty rats were randomly divided into three groups: group 1, control group; group 2, rats received CP in a dose of 7 mg/kg/day for 5 consecutive days; group 3, CP was injected at 7 mg/kg per day for 5 consecutive days, and, on the 6th day of the experiment, rats were treated with SSC. Forty days after receiving the last dose of CP, rats were euthanized under anesthesia; testes were collected, and gene expression using real-time polymerase chain reaction for P53, Bax, caspase 9 and cytochrome c, testicular histological findings and oxidative status were determined. RESULTS: Administration of cisplatin caused significant increases in malondialdehyde levels, Bax and caspase 9 genes expression levels concomitant with significant decreases in anti-oxidant enzyme activities, p53 and cytochrome c gene expression levels, along with some histopathological lesions in testicular tissue. SCC attenuated the disturbance in oxidant/anti-oxidant status and testicular apoptosis; this is associated with improvements in the histopathological view of the testicular tissue. CONCLUSIONS: The current study highlights evidence that the SCC has anti-oxidative and anti-apoptotic properties that could reverse CP-induced testicular toxicity, in addition to their role in spermatogenesis.

Association of angiotensin II type I and type II receptor genes polymorphisms with the presence of premature coronary disease and metabolic syndrome.

Premature coronary artery disease (PCAD) is known to have a particularly strong genetic component. We aimed to investigate the association between angiotensin II receptor type 1 (ATR1) or type II (ATR2) genes polymorphisms and PCAD with or without metabolic syndrome in males. 132 male patients with PCAD and 132 controls were included in the study. ATR1 and ATR2 genes polymorphisms were analyzed by polymerase chain reaction. The present study revealed that ATR1 CC genotype and ATR2 G allele increased the risk of PCAD by 2.9 and 1.3 respectively as well as they increased susceptibility to metabolic syndrome by 4.5 and 2.3 respectively. The present study proved that diabetes, smoking, obesity, total cholesterol, triglycerides, LDLc and HDLc were independent risk factors for the development of PCAD. We concluded that ATR1 CC genotype and ATR2 G allele increased the susceptibility of Egyptian males to have PCAD. The increased susceptibility to have metabolic syndrome could be one of the mechanisms leading to the development of PCAD in subjects carrying one or both of these polymorphisms.

Metagenomic analysis of fecal samples in colorectal cancer Egyptians patients post colectomy: A pilot study.

One of the most prevalent malignancies that significantly affects world health is colorectal cancer (CRC). While genetics are involved in a portion of CRC patients, most cases are sporadic. The microbiome composition could be a new source of tumor initiation and progression. This research was conducted to investigate the microbiota composition of CRC patients post colectomy at taxonomic and functional levels. Using a next-generation sequencing approach, using an Illumina Novaseq 6000, the fecal samples of 13 patients were analyzed and the obtained data was subjected to a bioinformatics analysis. The bacterial abundance and uniqueness varied in CRC patients alongside differences in bacterial counts between patients. Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, and Fusobacterium nucleatum were among the pro-cancerous microorganisms found. Concurrently, bacteria linked to CRC progression were detected that have been previously linked to metastasis and recurrence. At the same time, probiotic bacteria such as Bifidobacterium dentium, Bifidobacterium bifidum, and Akkermansia muciniphila increased in abundance after colectomies. Additionally, numerous pathways were deferentially enriched in CRC, which emerged from functional pathways based on bacterial shotgun data. CRC-specific microbiome signatures include an altered bacterial composition. Our research showed that microbial biomarkers could be more usefully employed to explore the link between gut microbiota and CRC using metagenomic techniques in the diagnosis, prognosis, and remission of CRC, thereby opening new avenues for CRC treatment.

Association of the interleukine-6 polymorphism with catheter-induced coronary artery spasm in Egyptians.

BACKGROUND: The role of coronary artery spasm (CAS) was extended beyond variant angina to ischemic heart disease in general, including effort angina, unstable angina, acute myocardial infarction (MI) and sudden death. It is difficult and cumbersome to examine CAS during coronary angiography. Risk factors for CAS include smoking and genetic polymorphisms. AIM: We aimed to investigate the association of the interleukin-6 (IL-6) polymorphism with catheter-induced CAS in Egyptian patients who undergo coronary angiography. METHODS: This is a case-control study. Two hundred patients with chronic coronary artery disease who underwent elective coronary angiography were included in the study. Patients were divided into two groups: the non-CAS group (100 patients) and the CAS group (100 patients). The subjects were genotyped to the -572 C>G (rs 1800796) polymorphism of the IL-6 gene by PCR-restriction fragment length polymorphism. RESULTS: We found that patients with CAS have more risk factors for atherosclerosis compared to those without CAS. Smoking, the IL-6 GG genotype, and the G allele were independent risk factors for CAS. CONCLUSION: We concluded that the GG genotype and G allele of the IL-6 gene are associated with CAS. Smoking, the GG genotype, and the G allele of the IL-6 gene are independent predictors of catheter-induced CAS.

The Diagnostic Value of Whole-Exome Sequencing in a Spectrum of Rare Neurological Disorders Associated with Cerebellar Atrophy.

Several neurological disorders, neurodevelopmental disorders, and neurodegenerative disorders have a genetic element with various clinical presentations ranging from mild to severe presentation. Neurological disorders are rare multifactorial disorders characterized by dysfunction and degeneration of synapses, neurons, and glial cells which are essential for movement, coordination, muscle strength, sensation, and cognition. The cerebellum might be involved at any time, either during development and maturation or later in life. Herein, we describe a spectrum of NDDs and NDs in seven patients from six Egyptian families. The core clinical and radiological features of our patients included dysmorphic features, neurodevelopmental delay or regression, gait abnormalities, skeletal deformities, visual impairment, seizures, and cerebellar atrophy. Previously unreported clinical phenotypic findings were recorded. Whole-exome sequencing (WES) was performed followed by an in silico analysis of the detected genetic variants' effect on the protein structure. Three novel variants were identified in three genes MFSD8, AGTPBP1, and APTX, and other previously reported three variants have been detected in "TPP1, AGTPBP1, and PCDHGC4" genes. In this cohort, we described the detailed unique phenotypic characteristics given the identified genetic profile in patients with neurological "neurodevelopmental disorders and neurodegenerative disorders" disorders associated with cerebellar atrophy, hence expanding the mutational spectrum of such disorders.

Role of DNA repair and cell cycle control genes in ovarian cancer susceptibility.

Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different cancer diseases. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. The aim of the present study was to evaluate the role of SNPs in three genes, XRCC2 (R188H), ERCC2 (K751Q) and CDKN1B (V109G) which are with moderate risk for ovarian cancer susceptibility in Egyptian women. We further investigated the potential combined effect of these genes variants on ovarian cancer risk. The three genes polymorphisms were characterized in 100 ovarian cancer Egyptian females and 100 healthy women by (RFLP-PCR) method in a case control study. Our results revealed that the frequencies of AC genotypes of ERCC2 (K751Q), and GG genotypes of CDKN1B (V109G) polymorphisms were significantly higher in EOC patients than in normal individual (P = 0.007, 0.02 respectively). The frequencies of AA genotype of XRCC2 (R188H) and CC genotype of ERCC2 (K751Q) were higher in EOC patients than in normal individual but without significance (P = 0.06, 0.38 respectively). Also, no association between any one of the three studied genes polymorphisms and the clinical characteristics of disease. The combination of GA (XRCC2) + AC (ERCC2) + GG (CDKN1B) was significantly associated with increased EOC risk. Also, the combination for GA (XRCC2) + AC (ERCC2) and the combination of AA (XRCC2) + CC (ERCC2) were significantly associated with increased EOC risk. There was significant difference in CA125 values between EOC and control Group (P < 0.001). Our results suggested that, XRCC2, ERCC2 and CDKN1B genes are important candidate genes for susceptibility to EOC. Also, gene-gene interaction between GA (XRCC2) + AC (ERCC2) + GG (CDKN1B) polymorphism may be associated with increased risk of EOCC in Egyptian women.

Association of Endothelial Nitric Oxide Synthase and Angiotensin-Converting Enzyme Genes Polymorphism With In-Sent Restenosis of Bare Metal Stents vs Drug-Eluting Stents in Egyptians.

Despite its unequivocal superiority compared with balloon angioplasty, coronary stenting did not abolish restenosis. We aimed to evaluate the associations between a common single nucleotide polymorphism occurring in endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) genes and the risk of in-stent restenosis (ISR) of bare metal stents vs drug-eluting stents (BMS vs DES) implanted in Egyptian patients. Two hundred patients who had coronary stenting were divided into group I (n = 98) who received a BMS and group II (n = 102) who received a DES. eNOS and ACE genes polymorphism were analyzed by polymerase chain reaction (PCR). We found that the GA and AA genotypes of the eNOS gene were associated with the ISR with both BMS and DES. However, the ACE gene was not associated with ISR. We concluded that eNOS gene polymorphism is associated with ISR. Hypertension, stent length, and AA genotype of the eNOS gene were found to be independent predictors of the occurrence of ISR after both BMS and DES use.

Synergism of CYP2R1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

CYP2R1 (25α-hydroxylase) catalyzes vitamin D(3) to 25-hydroxyvitamin D(3), while the CYP27B1 (1α-hydroxylase) catalyzes the 25(OH)D(3) to 1, 25(OH)(2)D(3). 1, 25(OH)(2)D(3) prevents the development of autoimmune diabetes. We aimed to investigate CYP2R1 and CYP27B1 genes polymorphisms and susceptibility to type 1 diabetes in children. One hundred and twenty type 1 diabetic patients and One hundred and twenty controls were genotyped for CYP2R1 (rs10741657) and CYP27B1 (rs10877012) polymorphism. GG genotype of CYP2R1 increased risk to develop type 1 diabetes, and CC genotype of CYP27B1 increased risk to develop type 1 diabetes. Our finding suggested that GG genotype of CYP2R1 polymorphism and/or CC genotype of CYP27B1 polymorphism increased the risk of developing of type 1 diabetes in Egyptian children. In addition there was a synergism between GG genotype of CYP2R1 and CC genotype of CYP27B1 regarding the risk of development of type 1 diabetes.

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction.

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF.

Association of CD4 enhancer gene polymorphisms with rheumatoid arthritis in Egyptian female patients.

CD4 is a candidate gene in autoimmune diseases, including rheumatoid arthritis (RA). Because the CD4 receptor is crucial for appropriate antigen responses of CD4+ T cells, changes in CD4 expression and CD4+ T-cell activity may influence tolerance or tissue destruction in autoimmune diseases and contribute to their risk. We analyzed two polymorphisms of the CD4 in 172 female Egyptian patients with RA and in 112 matched healthy control. Genotyping of CD4-11743 and CD4-10845 was determined by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). Subjects with the CC genotype of CD4-11743 were significantly more likely to develop RA (OR = 2.7, P = 0.03) and more likely to have sever RA (OR = 2.7, P = 0.024). Carrier of A allele of CD4-10845 was significantly more likely to develop sever RA (OR = 3.7, P = 0.000). CD4-11743 genetic polymorphisms are associated with the susceptibility and severity of RA, and CD4-10845 genetic polymorphisms are associated with the severity of RA.