MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis.

PURPOSE: The role of the Sirutin 1 (SIRT1) and MicroRNA-34 a (miR-34a) in endometriosis and the extent to which the miR-34a/SIRT1/p53 signaling pathway is involved in its pathogenesis is unclear, so we aimed to investigate the expression of miRNA 34-a, SIRT1, Forkhead boxO (FoxO-1), p53 and other apoptotic markers in endometrial tissue of women with endometriosis in order to better understand their role and the mechanisms of their actions in the pathogenesis of such disease and if it is related to apoptosis or not. METHODS: Ectopic and eutopic endometriotic tissues were collected from seventy women with endometriosis while normal endometrial tissues were obtained from 40 fertile women without endometriosis and then gene expression of SIRT-1, miR-34a,p53, Bax, Bcl-2, Bcl-xL and FoxO-1 were measured using RT-PCR. RESULTS: We detected that SIRT-1 and Bcl-xL genes expressions was significantly up-regulated while miRNA34-a,p53, Bax, Bcl-2 and FoxO-1 were down-regulated in endometrial tissue of endometriotic patients compared to that of those without endometriosis. There was an inverse relationship between SIRT-1a, Bcl-xL genes expressions and miR-34a, p53, Bax, Bcl-2 expressions as well as FoxO-1 expression. These results imply that miR-34a might regulate p53 through SIRT-1 and subsequently FoxO-1 expression in endometriotic tissue, and so it can contribute to the pathogenesis of endometriosis by decreasing the naturally occurring apoptosis in endometrium. CONCLUSION: This study may provide a potential biomarker for endometriosis therapeutics. Identification of target genes downstream of these transcriptional factors would allow better understanding of their respective roles in the pathogenesis of endometriosis.

Circulating Cell Free Nuclear DNA, Mitochondrial DNA and Global DNA Methylation: Potential Noninvasive Biomarkers for Breast Cancer Diagnosis.

Eighty seven women with benign breast lesion, 120 patients with breast cancer (BC) and one hundred controls were included in the study. Quantification of mtDNA and nDNA was done by qPCR. Global DNA methylation was measured using ELISA. Circulating cell-free nDNA and mtDNA were significantly elevated in BC and benign breast lesions patients. Global methylation was significantly low in BC patients. Combining the studied parameters in one panel, nDNA/mtDNA/hypomethylation, improved their sensitivity in detecting BC to reach 92.5%. Circulating cell-free nDNA, mtDNA and global DNA hypomethylation can be used as diagnostic and prognostic markers for BC.

Relationship Between Heat Shock Protein Expression and Obesity With and Without Metabolic Syndrome.

Background: Obesity is considered a chronic inflammatory disease in which the physiological mechanism responsible for reducing inflammation is weakened, prompting low-grade inflammation throughout the body. One of the key stress response systems that is dysregulated in obesity is the heat shock response, which is a critical defense mechanism that is activated in stressful conditions. Obesity is primary to metabolic syndrome (MetS) as it appears to lead to the increase in other MetS risk factors. Aim of the Study: We aimed to investigate the different expression levels of intracellular heat shock protein (iHSP) 70 and iHSP27 in obese patients with and without MetS and compare these levels to those of a lean control group. Patients and Methods: One hundred ten lean subjects were compared with 44 obese subjects without MetS and 56 obese subjects with MetS. HSP70 and HSP27 mRNA expression levels were measured by quantitative real-time polymerase chain reaction. Results: iHSP70 mRNA expression was significantly higher in obese subjects without MetS than in lean subjects (p = 0.04), whereas iHSP70 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS (p = 0.02) as well as in those in the lean group (p = 0.03). iHSP27 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS and in lean subjects (p = 0.037 and 0.031, respectively). Conclusion: We conclude that the intracellular expression levels of HSP70 and HSP27 may play an important role in the pathogenesis of MetS.

Protective effects of curcumin and silymarin against paracetamol induced hepatotoxicity in adult male albino rats.

BACKGROUND: Acute paracetamol (PCM) toxicity is a clinical problem; can result in a serious liver injury that finally may progress to acute liver failure. Curcumin (CUR) is a prevalent natural compound that can maintain prooxidant/antioxidant balance and thus can help in liver protection; also, Silymarin (SL) is a traditional antioxidant herb, used to treat liver disorders through scavenging free radicals. This study aimed to illustrate the histological, biochemical and molecular changes induced by acute PCM overdose on rats' liver to elucidate the effectiveness of CUR compared to SL in alleviating such changes. MATERIALS AND METHODS: Male Wister Albino rats were divided into 6 groups each comprising 23 rats: control group, curcumin (CUR) treated group received (100 mg CUR/ kg), silymarin treated group received (100 mg SL/kg) for 7 successive days. Paracetamol (PCM) exposed group administered a single dose of PCM (200 mg/kg orally on 8th day). PCM + CUR group and PCM + SL group pretreated with CUR and SL respectively for 7 days then received single PCM dose (200 mg/kg) on the 8th day. Blood and liver tissues were collected for biochemical, histopathological and immunohistochemical analyses using anti-p53 antibody. In addition, real time polymerase chain reaction (RT- PCR) was used to measure Bax, bcl2 and Peroxisome proliferator-activated receptor-gamma (PPAR γ) mRNA expression levels. RESULTS: In the paracetamol overdose group, the liver architecture showed necrotic changes, hydropic degeneration, congestion and dilatation of central veins. This hepatocellular damage was confirmed by a significant increase of AST, ALT levels and by an apparent increase in the number of p53 stained cells. PCM toxicity showed significant elevation of total oxidant status (TOS), oxidant status index (OSI) and decreased total antioxidant capacity (TAC) compared to controls (p < 0.001). Gene expression analysis showed that PCM caused an elevation of bcl2 and a reduction of both Bax and PPARγ mRNA expression. The histological alternation in the liver architecture was markedly improved in (PCM + CUR) group compared to (PCM+ SL) group, with an obvious decrease in the number of P53 stained cells. CUR pretreatment inhibited the elevation of TOS and OSI as well as the reduction of TAC caused by PCM toxicity compared to (PCM + SL) group. CONCLUSION: Both SL and CUR pretreatment prevented the toxic effects of PCM, but CUR is more effective than SL in ameliorating acute PCM induced hepatotoxicity.

Effect of negative pressure wound therapy on molecular markers in diabetic foot ulcers.

Diabetic foot ulcers are one of the most common complications of diabetes with high morbidity and mortality. Negative pressure wound therapy (NPWT) is one of the treatment modalities that facilitates the wound healing process; however, its molecular mechanism remains unclear. The aim of this study was to investigate the mechanism of action of NPWT in the treatment of diabetic foot ulcers via measuring the tissue expression of genes related to the wound healing process. The study included 40 patients with diabetic foot ulceration, 20 of them received NPWT and the other 20 were a control group treated with advanced moist therapy. Granulation tissue biopsies were obtained before and 10 days after treatment in both groups and subjected to real-time polymerase chain reaction to measure the mRNA expression of TGF-ß1, VEGF, TNF-α, IL-1ß, MMP-1, MMP-9 and TIMP-1 which are involved in the wound healing pathway. After 10 days of treatment with NPWT, the mRNA levels of IL-1ß, TNF-α, MMP-1, and MMP-9 were significantly downregulated, while the levels of VEGF, TGF-ß1 and TIMP-1 were significantly increased. Our study demonstrated that NPWT promotes wound healing in diabetic foot ulcers possibly by affecting growth factors, inflammatory cytokines, and matrix metalloproteinases.

Promoter Methylation of RASSF1A Gene in Egyptian Patients with Ovarian Cancer.

Ovarian malignancy is diagnosed in nearly a fourth of a million women internationally every year. Methylation of RASSF1A tumor suppressor gene prompts its inactivation in diseases. In this study, the RASSF1A promoter methylation was detected by methylated-specific PCR and investigated serum RASSF1A protein level through enzyme-linked immunosorbant assay in 160 Egyptian patients with ovarian cancer and 160 healthy controls. The present work proved that there was a higher frequency of RASSF1A methylation and a decrease in its serum level in patients with ovarian cancer compared to controls as well as in the high-grade tumor patients compared to low grade ones and also in advanced ovarian tumor stage compared to early stages. Our study exhibited that RASSF1A promoter hypermethylation and its protein levels may be a reliable and sensitive tool for diagnosing and monitoring of ovarian malignancy patients.

Therapeutic effect of spermatogonial stem cell on testicular damage caused by lead in rats.

OBJECTIVE: To investigate the possible therapeutic effect of spermatogonial stem cells (SSCs) on lead-induced apoptosis and consequently infertility in adult male rats. MATERIALS AND METHODS: Sixty-six Sprague Dawley adult male rats were divided into three groups: control group, lead (Pb) acetate exposed group received (20mg Pb/kg) for 3weeks, and SSCs treated group. Each group included twenty-two rats. Serum testosterone level, 3 beta-hydroxysteroid dehydrogenase (3ß-HSD), 17 beta-hydroxysteroid dehydrogenase (17ß-HSD), proliferating cell nuclear antigen (PCNA) genes expression by RT-PCR, caspase 3 expression by immunohistochemistry and testicular histological findings were tested. RESULTS: Pb acetate exposed rats showed a significant decrease in the epididymal sperm count, motility, viability, serum testosterone level and testicular expression of 3ß-HSD, 17ß-HSD and PCNA compared to the control group, while treatment with SSCs attenuated Pb acetate induced decrease for these variables. Moreover, the increasing apoptosis of germinal cells as well as the high expression of caspase-3 induced by Pb acetate was reduced by SSCs treatment. CONCLUSION: SSCs exhibited therapeutic effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF-ß therapy.

Interferon (IFN)-ß is one of the disease modifying drugs used in the treatment of multiple sclerosis. A predictive marker that indicates good or poor response to the treatment is highly desirable. We aimed to investigate the relation between the immune response genes receptors (IFNAR1, IFNAR2, and CCR5) expression and their polymorhic variants and multiple sclerosis (MS) susceptibility as well as the response to IFN-ß therapy. The immune response genes receptors expression and genotyping were analyzed in 80 patients with MS, treated with IFN-ß and in 110 healthy controls. There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group. Also, the level of IFNAR1, IFNAR2, and CCR5 mRNA expression was found to be significantly lower in the responders than nonresponders. Carriers of IFNAR1 18417 C/C genotype and C allele had an increased risk of developing MS. There was a significant relation between CCR5 Δ32 allele and IFN-ß treatment response in MS patients. Our results highlighted the significance of IFNAR and CCR5 genes in multiple sclerosis risk and the response to IFN-ß therapy. © 2016 IUBMB Life, 68(9):727-734, 2016.

Association of Insulin-Like Growth Factor-1 Gene Polymorphisms with Different Types of Myopia in Egyptian Patients.

AIMS: To investigate the effect of the insulin-like growth factor-1 (IGF-1) gene's rs6214 and rs5742632 polymorphisms on IGF-1 expression levels and their association with different types of myopia in Egyptian patients. METHODS: A case-control format was used that included 272 patients with myopia and 136 controls. The IGF-1 gene rs6214 and rs5742632 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses. IGF-1 levels were measured by an enzyme-linked immunosorbent assay. RESULTS: In patients with high-grade myopia, the frequencies of the IGF-1 rs6214 GA and AA genotypes, and the A allele were significantly increased compared to the control group: 41.9% vs. 33.8%, 17.7% vs. 8.9%, and 38.9% vs. 25.7%, respectively. Subjects with the GA and AA genotypes and carriers of A allele were significantly more likely to have high-grade myopia: odds ratios (OR) = 1.75, 95% confidence interval (CI) = 1.03-2.9, and p = 0.03; OR = 2.8, 95% CI = 1.3-6.0, and p = 0.003; and OR = 1.8, 95% CI = 1.25-2.61, and p = 0.001, respectively. A nonsignificant association of the IGF-1 gene rs5742632 polymorphism with the two myopia groups was also observed. The IGF-1 levels were significantly increased in patients with high-grade myopia and simple myopia compared to the control group (p < 0.05). In addition, our results showed a nonsignificant association of the IGF-1 (rs6214-rs5742632) haplotype with either simple myopia or high-grade myopia. CONCLUSIONS: We found a significant association of the IGF-1 gene rs6214 polymorphism in Egyptian patients with simple myopia and high-grade myopia. IGF-1 levels were significantly increased in relation to the IGF-1 rs6214 genotypes, while a nonsignificant association was found between IGF-1 level and the IGF-1 (rs5742632) genotypes.

Role of MicroRNA 126 in screening, diagnosis, and prognosis of diabetic patients in Egypt.

MicroRNAs (miRNAs), family of non-coding small RNAs, play a vital role in the regulation of blood glucose level. We aimed to investigate the relation of serum miRNA-126 expression with impaired glucose tolerance as well as type 2 diabetes mellitus (T2DM) patients with and without complications. One hundred healthy controls, eighty-six patients with IGT, and one hundred patients with T2DM were recruited in this study. Serum miRNA-126 expression was assessed by quantitative real-time polymerase chain reaction. We found a significant decrease of serum miRNA-126 expression between IGT patients as well as diabetic patients when both compared with controls and between diabetic patients compared to IGT patients. A significant decrease of serum miRNA-126 expression was detected in diabetic patients with complications compared to those without evident complications especially those with diabetic macrovascular complications and diabetic retinopathy. Serum microRNA-126 expression could be a good marker for diagnosis of IGT and T2DM as well as for monitoring the outcomes of such disease. © 2016 IUBMB Life, 68(6):452-458, 2016.

Interleukin-17 and leptin genes polymorphisms and their levels in relation to recurrent pregnancy loss in Egyptian females.

Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A (rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women's serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one.

COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis.

The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis.

Metallothionein 2A expression and its relation to different clinical stages and grades of breast cancer in Egyptian patients.

OBJECTIVE: To assess the relation of blood MT-2A expression, serum zinc, copper, Cu/Zn ratio, total antioxidant status (TAS), total oxidant status (TOS) and oxidant status index (OSI) with benign and malignant breast tumors, also, their relation to different clinical stages and grades of breast cancer. MATERIAL AND METHODS: Unrelated 199 female patients with breast tumor and 120 healthy controls were enrolled in this study. Metallothionein-2A (MT-2A) expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR). Serum MT-2A levels were measured by ELISA. Serum copper (Cu) and Zinc (Zn) concentrations were determined by atomic absorption spectrophotometry. Serum TOS and TAS levels were measured colorimetrically. RESULTS: Our study demonstrated that blood metallothionein-2A mRNA level, serum MT-2A, copper, Cu/Zn ratio, total oxidant status and oxidant status index were significantly increased, while, serum zinc level and total antioxidant status were significantly decreased in patients with breast cancer and benign breast disease as compared to controls and in breast cancer group as compared to the benign one. CONCLUSIONS: Blood metallothionein-2A expression and serum MT-2A levels could be important prognostic indices of less differentiated, more aggressive breast cancer phenotype. Disturbance of copper, zinc and oxidative stress status might contribute to the pathogenesis of breast tumor and could be useful biomarkers for diagnosing and monitoring such disease.

Influence of interleukin-1 gene cluster polymorphisms on the susceptibility and outcomes of acute stroke in Egyptian patients.

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. A growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischemia. The objective of this study is to investigate the influence of IL-1 cluster gene polymorphisms on the susceptibility of acute stroke and its outcomes in Egyptian patient. 320 patients with new or recurrent stroke [176 with atherothrombotic cerebral infarction, 79 with intracerebral hemorrhage (ICH), and 65 with subarachnoid hemorrhage (SAH)] and 320 controls were included in the study. IL-1b -511, IL-1a -889, and IL-1RN VNTR polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism. Serum level of IL-1 was measured by enzyme linked immunosorbent assay. All patients were followed for neurological and functional impairments 7 days, 1, 3 and 6 months after the onset of the stroke. We found that IL-1b -511 gene polymorphisms were significantly increased in patients with atherothrombotic, intracerebral, and SAH. Subjects with IL-1a -889 CT and TT genotypes were significantly more likely to have atherothrombotic infarction. Both IL-1b -511, IL-1a -889 genes polymorphisms were significantly more likely to have severe neurological and functional impairment, while IL-1RN 2/2 genotype was significantly decreased in atherothrombotic infarction and ICH groups and showed less severe neurological and functional impairments 7 days, 1, 3, and 6 months after the onset of the stroke compared with carriers of the IL1RN 1/1 and 1/2 genotypes. We concluded that IL-1 cluster gene polymorphisms were associated with risk of acute stroke. IL-1b, IL-1a gene polymorphisms were associated with more severe functional and neurological impairments, while IL-1RN VNTR polymorphisms were associated with good outcomes.

Renalase gene polymorphism and epinephrine level in chronic kidney disease.

Chronic kidney disease (CKD) is an important public health problem. Patients with end-stage renal disease have a significant renalase deficiency, which could be one of the mechanisms explaining high prevalence of hypertension in these patients. The aim of this study was to investigate the possible association of renalase gene (rs2296545) polymorphism with normotensive and hypertensive CKD in sampled Egyptian patients and to determine the effect of such polymorphism on epinephrine level. Renalase gene (rs2296545) polymorphism was genotyped in 178 patients with CKD (83 normotensive and 95 hypertensive nephrosclerosis) and 178 normal healthy adults using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epinephrine level was measured by HPLC method. We found an association of renalase (rs2296545) CC genotype and C allele with CKD. Also, the epinephrine level was significantly increased in normotensive and hypertensive nephrosclerosis patients as compared to controls. CKD patients with CC genotype showed significant high epinephrine level as compared to CG and GG genotypes.

Relation of PAI-1 and TPA genes polymorphisms to acute myocardial infarction and its outcomes in Egyptian patients.

Endogenous fibrinolysis is a protective mechanism against arterial thrombotic occlusion, which would otherwise lead to permanent tissue damage as acute myocardial infarction (AMI). We aimed to investigate the association of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA) genes polymorphisms with myocardial infarction and its outcomes in Egyptian patients. 184 patients with AMI and 184 controls were included in the study. PAI-1 and TPA genes polymorphisms were analyzed by polymerase chain reaction. All patients were followed for AMI complications during their hospitalization. We found a significant association among TPA ID, II genotypes, and I allele and increased risk of AMI by 2.1, 3.2, and 1.9 fold, respectively. Also, the frequencies of PAI-1 4G/4G genotype and 4G allele were significantly increased in patients with AMI as compared to the control group. Furthermore, AMI patients with PAI-1 4G/4G genotype were significantly more likely to have morbidity and mortality complications as compared to AMI patients without complications (P = 0.00 and 0.048, respectively). We concluded that 4G/4G genotype and 4G allele of the PAI-1 gene are associated with risk of AMI and its morbidity. The PAI-1 4G/4G genotype is associated with mortality of AMI. There is also an association between TPA ID, II genotypes, and I allele with increased risk of AMI.

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.

MTHFR C677T and A1298C gene polymorphisms and their relation to homocysteine level in Egyptian children with congenital heart diseases.

OBJECTIVE: To investigate the association of combined MTHFR C677T and A1298C gene polymorphisms with congenital heart diseases (CHD) in Egyptian children and their mothers and to determine their effect on homocysteine level in these children. MATERIAL AND METHODS: MTHFR C677T and A1298C polymorphisms were genotyped in 160 Egyptian children (80 patients with CHD and 80 healthy controls) and their mothers using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while, homocysteine (Hcy) level was measured optically by enzymatic method. RESULTS: We found that MTHFR 677TT genotype, T allele, 1298CC genotype, and C allele were associated with 2.61, 2.0, 2.91 and 1.99 fold increased risk of CHD in Egyptian children respectively. Furthermore, the frequencies of MTHFR 1298AC and CC genotypes and C allele significantly increased in mothers with CHD affected children. The homocysteine levels were significantly increased in MTHFR 677TT and 1298CC genotypes in children with CHD. CONCLUSIONS: Our study demonstrated an association of MTHFR A1298C polymorphisms with CHD in Egyptian children and their mothers, while, MTHFR C677T polymorphisms were significantly associated with the risk of CHD in the children only. An association between combined MTHFR A1298C and C677T polymorphisms and CHD was recorded in the children and their mothers. Also, homocysteine levels were significantly increased with both MTHFR 677TT and 1298CC genotypes in Egyptian children with CHD.

Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder.

Catechol-O-methyltransferase (COMT) plays an important role in the catabolism of brain dopamine and norepinephrine, which have been implicated in the pathogenesis of Autism spectrum disorder (ASD) as well as in other neuropsychatric disorders. We aimed to investigate the association of COMT Val158Met gene polymorphism with ASD and to examine the influence of such genotypes on hyperactivity symptoms in ASD patients. Eighty ASD patients (mean age 9 ± 1.9 years) and 100 control children (mean age 8.9 ± 1.9 years) were examined. COMT Val58Met polymorphism was genotyped using Tetra-primer ARMS-PCR method. The clinical diagnosis of ASD and ADHD were confirmed according to the DSM-IV criteria for research. We found no significant difference in genotypes or alleles' frequencies of COMT Val158Met polymorphism between ASD patients and control group. There was a significant association between COMT (Val/Val) genotype and both increasing CARS (p=0.001) and hyperactivity scores (p=0.006). Regarding Conner's Score, the DSM-IV hyperactive impulsive were significantly higher in Val/Val genotype than both Met/Val and Met/Met genotypes (p=0.03). Our data suggested an association between COMT Val58Met polymorphism and hyperactivity symptoms in Egyptian children with ASD.

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.