Background: DKK3 and SOX17, antagonists of Wnt/β-catenin pathway, function as tumor suppressor genes. Promoter methylation of DKK3 and SOX17 genes has been shown in many cancers. Several epigenetic alterations as DNA methylation are reported to be associated with the risk of breast cancer in relatives of breast cancer patients. Objective: This study aimed to explore the relationships between DKK3 and SOX17 gene methylation with family history and clinicopathological characters of breast cancer. Subjects and Methods: A total of 90 females were selected, 30 with breast cancer, 60 age-matched cancer-free subjects; 30 with (high risk group) and 30 without (control group) family history of breast cancer. Sybr green-based quantitative methylation-specific PCR was used for the determination of DKK3 and SOX17 methylation levels. Results: Significant variations were observed within DKK3 and SOX17 methylation percentage between the breast cancer, high risk and control groups (p0.001, p=0.002, respectively). Interestingly, SOX17 methylation was not related to any of tumor characteristics or family history of breast cancer, however, SOX17 methylation percentage had a positive correlation with the BMI(r=0.28, p=0.045) and a negative correlation with the age at diagnosis (r = -0.28, p=0.019). DKK3 methylation percentage was significantly higher in patients with postmenopausal state or negative progesterone receptor immunostaining (p=0.046, p=0.024, respectively). Through linear regression analysis, DKK3 methylation was associated with lymph node grade and negative progesterone receptor. Receiver operating characteristic curve analysis showed that DKK3 methylation had 61.7% specificity and 83.3% sensitivity at cutoff 68.8 % and area under the curve 0.803 (p0.001, 95% CI=0.703 - 0.903), while, SOX17 methylation had the same sensitivity as DKK3, but higher specificity 76.6% at cutoff point 93.6% with area under curve 0.803 (p0.001,95% CI =0.738 -0.925). Conclusion: DKK3 methylation shows a higher family history of breast cancer than SOX17 methylation. SOX17 methylation at a higher methylation percentage has better sensitivity for the diagnosis of breast cancer. These data suggest that methylation of the Wnt pathway antagonist may be associated with family history and clinicopathological characters of breast cancer. Analysis of DKK3 and SOX17 methylation in the breast tissue of females at risk of breast cancer could provide more information about relationships with risk factors of breast cancer. .

Background: DKK3 and SOX17, antagonists of Wnt/β-catenin pathway, function as tumor suppressor genes. Promoter methylation of DKK3 and SOX17 genes has been shown in many cancers. Several epigenetic alterations as DNA methylation are reported to be associated with the risk of breast cancer in relatives of breast cancer patients. Objective: This study aimed to explore the relationships between DKK3 and SOX17 gene methylation with family history and clinicopathological characters of breast cancer. Subjects and Methods: A total of 90 females were selected, 30 with breast cancer, 60 age-matched cancer-free subjects; 30 with (high risk group) and 30 without (control group) family history of breast cancer. Sybr green-based quantitative methylation-specific PCR was used for the determination of DKK3 and SOX17 methylation levels. Results: Significant variations were observed within DKK3 and SOX17 methylation percentage between the breast cancer, high risk and control groups (p0.001, p=0.002, respectively). Interestingly, SOX17 methylation was not related to any of tumor characteristics or family history of breast cancer, however, SOX17 methylation percentage had a positive correlation with the BMI(r=0.28, p=0.045) and a negative correlation with the age at diagnosis (r = -0.28, p=0.019). DKK3 methylation percentage was significantly higher in patients with postmenopausal state or negative progesterone receptor immunostaining (p=0.046, p=0.024, respectively). Through linear regression analysis, DKK3 methylation was associated with lymph node grade and negative progesterone receptor. Receiver operating characteristic curve analysis showed that DKK3 methylation had 61.7% specificity and 83.3% sensitivity at cutoff 68.8 % and area under the curve 0.803 (p0.001, 95% CI=0.703 - 0.903), while, SOX17 methylation had the same sensitivity as DKK3, but higher specificity 76.6% at cutoff point 93.6% with area under curve 0.803 (p0.001,95% CI =0.738 -0.925). Conclusion: DKK3 methylation shows a higher family history of breast cancer than SOX17 methylation. SOX17 methylation at a higher methylation percentage has better sensitivity for the diagnosis of breast cancer. These data suggest that methylation of the Wnt pathway antagonist may be associated with family history and clinicopathological characters of breast cancer. Analysis of DKK3 and SOX17 methylation in the breast tissue of females at risk of breast cancer could provide more information about relationships with risk factors of breast cancer. .

Background: DKK3 and SOX17, antagonists of Wnt/β-catenin pathway, function as tumor suppressor genes. Promoter methylation of DKK3 and SOX17 genes has been shown in many cancers. Several epigenetic alterations as DNA methylation are reported to be associated with the risk of breast cancer in relatives of breast cancer patients. Objective: This study aimed to explore the relationships between DKK3 and SOX17 gene methylation with family history and clinicopathological characters of breast cancer. Subjects and Methods: A total of 90 females were selected, 30 with breast cancer, 60 age-matched cancer-free subjects; 30 with (high risk group) and 30 without (control group) family history of breast cancer. Sybr green-based quantitative methylation-specific PCR was used for the determination of DKK3 and SOX17 methylation levels. Results: Significant variations were observed within DKK3 and SOX17 methylation percentage between the breast cancer, high risk and control groups (p0.001, p=0.002, respectively). Interestingly, SOX17 methylation was not related to any of tumor characteristics or family history of breast cancer, however, SOX17 methylation percentage had a positive correlation with the BMI(r=0.28, p=0.045) and a negative correlation with the age at diagnosis (r = -0.28, p=0.019). DKK3 methylation percentage was significantly higher in patients with postmenopausal state or negative progesterone receptor immunostaining (p=0.046, p=0.024, respectively). Through linear regression analysis, DKK3 methylation was associated with lymph node grade and negative progesterone receptor. Receiver operating characteristic curve analysis showed that DKK3 methylation had 61.7% specificity and 83.3% sensitivity at cutoff 68.8 % and area under the curve 0.803 (p0.001, 95% CI=0.703 - 0.903), while, SOX17 methylation had the same sensitivity as DKK3, but higher specificity 76.6% at cutoff point 93.6% with area under curve 0.803 (p0.001,95% CI =0.738 -0.925). Conclusion: DKK3 methylation shows a higher family history of breast cancer than SOX17 methylation. SOX17 methylation at a higher methylation percentage has better sensitivity for the diagnosis of breast cancer. These data suggest that methylation of the Wnt pathway antagonist may be associated with family history and clinicopathological characters of breast cancer. Analysis of DKK3 and SOX17 methylation in the breast tissue of females at risk of breast cancer could provide more information about relationships with risk factors of breast cancer. .

AIM: To investigate ENDRA rs5333 gene polymorphism distribution in idiopathic nephrotic syndrome (INS) and to analyze their association with response to steroid therapy, and biochemical markers of INS. SUBJECTS & METHODS: The PCR-restriction fragment length polymorphism was used to analyze ENDRA rs5333 polymorphism in 100 children with idiopathic nephrotic syndrome (INS) and 100 healthy children. Plasma endothelin-1 were measured by ELISA. RESULTS: The ENDRA rs5333 gene polymorphism was not associated with risk of INS. The frequency of minor allele (C) was significantly higher in the steroid resistant nephrotic syndrome group than the steroid sensitive group. The CC and TC mutant variants were associated with higher plasma levels of cholesterol, albumin, urea and 24-h urinary protein, but were not associated with risk of hypertension. The endothelin-1 plasma level was higher in INS than control and in steroid resistant nephrotic syndrome group when compared with steroid sensitive group cases. CONCLUSION: The ENDRA rs5333 gene polymorphism may be associated with genetic predisposition to steroid resistance in INS Egyptian children.

AIM: To investigate ENDRA rs5333 gene polymorphism distribution in idiopathic nephrotic syndrome (INS) and to analyze their association with response to steroid therapy, and biochemical markers of INS. SUBJECTS & METHODS: The PCR-restriction fragment length polymorphism was used to analyze ENDRA rs5333 polymorphism in 100 children with idiopathic nephrotic syndrome (INS) and 100 healthy children. Plasma endothelin-1 were measured by ELISA. RESULTS: The ENDRA rs5333 gene polymorphism was not associated with risk of INS. The frequency of minor allele (C) was significantly higher in the steroid resistant nephrotic syndrome group than the steroid sensitive group. The CC and TC mutant variants were associated with higher plasma levels of cholesterol, albumin, urea and 24-h urinary protein, but were not associated with risk of hypertension. The endothelin-1 plasma level was higher in INS than control and in steroid resistant nephrotic syndrome group when compared with steroid sensitive group cases. CONCLUSION: The ENDRA rs5333 gene polymorphism may be associated with genetic predisposition to steroid resistance in INS Egyptian children.

AIM: To investigate ENDRA rs5333 gene polymorphism distribution in idiopathic nephrotic syndrome (INS) and to analyze their association with response to steroid therapy, and biochemical markers of INS. SUBJECTS & METHODS: The PCR-restriction fragment length polymorphism was used to analyze ENDRA rs5333 polymorphism in 100 children with idiopathic nephrotic syndrome (INS) and 100 healthy children. Plasma endothelin-1 were measured by ELISA. RESULTS: The ENDRA rs5333 gene polymorphism was not associated with risk of INS. The frequency of minor allele (C) was significantly higher in the steroid resistant nephrotic syndrome group than the steroid sensitive group. The CC and TC mutant variants were associated with higher plasma levels of cholesterol, albumin, urea and 24-h urinary protein, but were not associated with risk of hypertension. The endothelin-1 plasma level was higher in INS than control and in steroid resistant nephrotic syndrome group when compared with steroid sensitive group cases. CONCLUSION: The ENDRA rs5333 gene polymorphism may be associated with genetic predisposition to steroid resistance in INS Egyptian children.

Background: Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular mortality (CV) in end stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate the relation of some inflammatory markers (as high-sensitive C-reactive protein (hs CRP) and interleukin-18 (IL-18) with LVH in children with ESRD on regular hemodialysis (HD). Methods: This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin, hs-CRP, IL-18, phosphorus, calcium, serum albumin and lipid profile were evaluated and correlated with LVH. Data were analyzed by using student’s t test, and logistic regression to determine the relationship between LVH and other variables. Results: LVH was present in 33 (66%) participants. Mean left ventricular mass index (LVMI) was 56.88±22.23 gm /m2.7. Concentric remodeling, concentric hypertrophy and eccentric hypertrophy were present in 4, 22 and 44% of the participants. In univariate analysis: children with LVH had significantly lower levels of hemoglobin and serum albumin but higher levels of hs- CRP, and IL-18 compared to those without LVH. On multivariate analysis: only hs-CRP, and IL-18 were significantly associated with LVH. Conclusions: This study shows that elevated hs-CRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high risk group and implementation of targeted anti-inflammatory therapies.

Background: Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular mortality (CV) in end stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate the relation of some inflammatory markers (as high-sensitive C-reactive protein (hs CRP) and interleukin-18 (IL-18) with LVH in children with ESRD on regular hemodialysis (HD). Methods: This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin, hs-CRP, IL-18, phosphorus, calcium, serum albumin and lipid profile were evaluated and correlated with LVH. Data were analyzed by using student’s t test, and logistic regression to determine the relationship between LVH and other variables. Results: LVH was present in 33 (66%) participants. Mean left ventricular mass index (LVMI) was 56.88±22.23 gm /m2.7. Concentric remodeling, concentric hypertrophy and eccentric hypertrophy were present in 4, 22 and 44% of the participants. In univariate analysis: children with LVH had significantly lower levels of hemoglobin and serum albumin but higher levels of hs- CRP, and IL-18 compared to those without LVH. On multivariate analysis: only hs-CRP, and IL-18 were significantly associated with LVH. Conclusions: This study shows that elevated hs-CRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high risk group and implementation of targeted anti-inflammatory therapies.

Background: Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular mortality (CV) in end stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate the relation of some inflammatory markers (as high-sensitive C-reactive protein (hs CRP) and interleukin-18 (IL-18) with LVH in children with ESRD on regular hemodialysis (HD). Methods: This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin, hs-CRP, IL-18, phosphorus, calcium, serum albumin and lipid profile were evaluated and correlated with LVH. Data were analyzed by using student’s t test, and logistic regression to determine the relationship between LVH and other variables. Results: LVH was present in 33 (66%) participants. Mean left ventricular mass index (LVMI) was 56.88±22.23 gm /m2.7. Concentric remodeling, concentric hypertrophy and eccentric hypertrophy were present in 4, 22 and 44% of the participants. In univariate analysis: children with LVH had significantly lower levels of hemoglobin and serum albumin but higher levels of hs- CRP, and IL-18 compared to those without LVH. On multivariate analysis: only hs-CRP, and IL-18 were significantly associated with LVH. Conclusions: This study shows that elevated hs-CRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high risk group and implementation of targeted anti-inflammatory therapies.

Background: DNA methylation is associated with the risk factors of breast cancer. However, the impact of the reproductive and non-reproductive risk factors of breast cancer on p14/ARF methylation is not well-known. Therefore, we investigated the relationships between p14/ARF methylation percentage and risk factors of breast cancer including age, family history, obesity, and reproductive risk factors in 120 breast cancer-free subjects; 60 women with a first-degree family history of breast cancer and 60 age-matched women with no family history of breast cancer. Extracted DNA from the whole blood was bisulfite-treated by EZ-DNA modification kit. Quantitative methylation of p14/ARF was analyzed by methylation-specific PCR then methylation percentage of p14/ARF was calculated. ‏ Results: P14/ARF methylation percentage was not related to any of the risk factors of breast cancer except age. Our study showed that p14/ARF methylation percentage was significantly higher in females with age ≥ 40 years than in females with age 40 years (p 0.001). Also, a positive significant correlation between the p14/ARF methylation percentage and age was detected (r= 0.285, p= 0.014). Furthermore, univariate regression analysis showed that the age is independently associated with high p14/ARF methylation percentage (β=1. 46, p=0.029)‏. Conclusion: Among healthy females, the age is strongly linked to the peripheral p14/ARF methylation percentage. The present study suggests that p14/ARF methylation is not associated with other breast cancer risk factors. These results need oncoming research on a large cohort to define the interactions between p14/ARF methylation and the risk factors of breast cancer.