Circadian clock gene expression and polymorphism in non-segmental vitiligo.

BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease with the damage of functioning epidermal melanocytes. Metabolic syndrome is associated with inflammatory skin diseases incorporating vitiligo. The circadian dysfunction triggers the pathogenesis of metabolic diseases, so our study aimed to determine the relationship between aryl hydrocarbon receptor nuclear translocator-like gene, a ligand-activated transcription factor and sensor of environmental chemicals, expression and polymorphism with non-segmental vitiligo, as well as its effect on lipid profile. METHODS: This case-control study was handled on 50 non-segmental vitiligo patients (generalized (12) and localized type (focal; 24 and acrofacial; 14)) and 50 matched controls. Each subject was proposed for full history taking, clinical examinations, serum lipid profile, and measurement of BMAL1 gene expression in the blood, and BMAL1 rs2279287 polymorphism of DNA extract from whole blood by real time-PCR. RESULTS: We identified that total cholesterol, triglyceride, and low-density lipoprotein were significantly higher, but high-density lipoprotein was significantly lower in non-segmental vitiligo patients than in the control group. A significant increase in circadian gene expression in non-segmental vitiligo patients was observed, with more detection of the BMAL1 T/C genotype (92%) than the T/T genotype. There was a significant positive relationship between the level of the circadian gene and the vitiligo patient's age, age of onset, and VIDA Score. The level of the circadian gene at Cutoff  ≥ 1.16 can predict the prognosis of vitiligo with a sensitivity of 78%, specificity of 84%, and accuracy of 81%. CONCLUSION: The circadian gene has an active role in the progress of non-segmental vitiligo and targeting this gene could have a significant impact on its management.

MicroRNA-29a and MicroRNA-124 as novel biomarkers for hepatocellular carcinoma.

BACKGROUND: Numerous microRNAs (miRNAs) have been observed to be abnormally expressed in cancer. Therefore, miRNA signatures could be potential noninvasive diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). AIMS: To correlate miRNA-29a and miRNA-124 expression levels with the clinical features and survival rates of HCC patients. METHODS: Serum miRNA expression in 150 samples (50 patients with HCC, 50 patients with liver cirrhosis, and 50 healthy controls) were quantified using real-time qRT-PCR. RESULTS: The expression levels of serum miRNA-29a were higher and the levels of miRNA-124 were lower in patients with HCC than in patients with liver cirrhosis and controls. ROC curve analysis showed promising accuracy for both miRNAs in distinguishing patients with HCC from those with liver cirrhosis. Levels of miRNA-29a were related to tumor number, size, stage, and outcome, whereas levels of miRNA-124 were related to vascular invasion. The overall survival rate of patients with low miRNA-29a expression was significantly higher than that of patients with high expression. Additionally, the multivariate analysis identified miRNA-29a as an independent prognostic variable. CONCLUSIONS: The investigated miRNAs showed acceptable accuracy in the diagnosis of HCC; therefore, both could be utilized as diagnostic biomarkers. Additionally, miRNA-29a could be used as a prognostic biomarker.

Relationship of steroid sex hormones with female sexual dysfunction in female patients having urinary incontinence.

To investigate serum estradiol, progesterone and dehydroepiandrosterone levels on FSD in females having urinary incontinence (UI), we studied 150 females [100 having UI (50 with FSD and 50 without FSD) and 50 controls]. There were significant lower estradiol and progesterone and higher DHEA serum levels in patients than controls (P = 0.001for all). In UI patients, females having sexual disruption had significantly low levels of estradiol (p = 0.001). Low estradiol serum level represented an isolated predictive factor for sexual dysfunction in incontinent female patients (p = 0.001). A low estradiol serum level might be a possible risk factor for FSD in women having UI.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo

Abstract Background: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty AcidBinding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. Objectives: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. Methods: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. Results: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). Study limitations: The small number of studied subjects. Conclusions: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo.

BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty Acid-Binding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. OBJECTIVES: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. METHODS: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. RESULTS: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). STUDY LIMITATIONS: The small number of studied subjects. CONCLUSIONS: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

The Role of LINC01564, RAMS11, CBX4 and TOP2A in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancers worldwide. Hepatitis C virus (HCV) infection remains a major risk factor for chronic liver disease, cirrhosis, and HCC. To understand the molecular pathogenesis of HCC in chronic HCV infection, many molecular markers are extensively studied, including long noncoding RNAs (lncRNA). Objective: To evaluate the expression levels of lncRNAs (LINC01564, RAMS11), CBX4, and TOP2A in patients with chronic HCV infection and patients with HCC on top of chronic HCV infection and correlate these levels with the clinicopathological features of HCC. Subjects and Methods: One hundred and fifty subjects were enrolled in this study and divided into three groups: group I included 50 patients with HCC on top of chronic hepatitis C (CHC), group II included 50 patients with CHC only, and group III included 50 healthy individuals as a control group. LncRNAs relative expression level was determined by RT-PCR. Results: lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in both patient groups compared to controls (p < 0.001*), with the highest levels in the HCC group compared with the CHC group. Additionally, these levels were significantly positively correlated with the clinicopathological features of HCC. Conclusions: The lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in CHC patients­in particular, patients with HCC. Thus, these circulatory lncRNAs may be able to serve as promising noninvasive diagnostic markers for HCC associated with viral C hepatitis.

Association of the myosin heavy chain 9 gene single nucleotide polymorphism with inflammatory bowel disease.

BACKGROUND: To date, the cause of inflammatory bowel disease (IBD) remains a mystery. A balance between cell proliferation and apoptosis maintains intestinal tissue homeostasis. Dissociation-induced myosin-actin contraction results in stem cell apoptosis. This study aiming to evaluate the influence of the myosin heavy chain 9 (MYH9) gene single nucleotide polymorphisms (SNPs) on inflammatory bowel disease. SUBJECTS: and methods: The study carried on eighty patients with IBD and seventy controls. All participants subjected to history taking, thorough physical examination, colonoscopy and laboratory investigations. Genotyping performed for rs4821480 and rs3752462 by SNP assay real-time PCR methods. RESULTS: On analyzing rs3752462 CT and TT genotypes were significantly more frequent in IBD patients as compared to controls with 4.6 fold increase in the risk of IBD. While on analyzing rs4821480, The TG and GG genotypes have significant increased distribution among the IBD patients as compared to the controls with 5.3 fold increase in the risk of IBD and higher prevalence of GG genotype in patients with low hemoglobin level and higher BMI. CONCLUSION: The rs3752462 T allele and rs4821480 G allele of MYH9 are associated with more susceptibility to IBD.

Genetic polymorphism of fibroblast growth factor receptor 2 and trinucleotide repeat-containing 9 influence the susceptibility to HCV-induced hepatocellular carcinoma.

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) and trinucleotide repeat-containing 9 (TRNC9) gene polymorphisms have been associated with some cancers. We aimed to assess the association of FGFR2 rs2981582 and TRNC9 rs12443621 polymorphisms with hepatocellular cancer risk. METHODS: One hundred patients with HCV-induced HCC, 100 patients with chronic HCV infection, and 100 controls were genotyped for FGFR2 rs2981582 and TNRC9 rs12443621 using allele-specific Real-Time PCR analysis. RESULTS: FGFR2 rs2981582 genotype TT was associated with increased risk of HCC when compared to controls (OR = 3.09, 95% CI = 1.24-7.68). However, it was significantly associated with a lower risk of HCC when using HCV patients as controls (OR = 0.21, 95% CI = 0.09-0.5), and T-allele of FGFR2 appears to be a protective allele against HCC in HCV patients (OR = 0.42, 95% CI = 0.21-0.85). While AG and GG genotypes of TNRC9 rs12443621 were linked with significantly increased risk of HCC (OR = 3.91, 95% CI = 2.02-7.6 and OR = 9.26, 95% CI = 3.21-26.7 respectively) and HCV patients carrying G allele were at increased risk of HCC by 2.7-fold. A significant high frequency of small tumor size and early-stage of HCC were observed in patients carrying FGFR2 rs2981582 genotype CT and TT (P = 0.029 and <0.001 respectively), while, TNRC9 rs12443621 genotype AG and GG were associated large tumor size and late-stage of HCC (P < 0.001 and 0.015 respectively). CONCLUSIONS: SNPs in rs2981582 for FGFR2 and rs12443621 for TNRC9 gene were associated with HCC susceptibility, suggesting their implication in hepatocarcinogenesis in chronically HCV-infected patients.

Relation of neuropeptide Y gene expression and genotyping with hypertension in chronic kidney disease.

OBJECTIVES: The prognosis of high-risk patients might be greatly ameliorated using genetic predisposition risk factors. Sympathetic activity and innate immunity related to neuropeptide Y function may be related to dyslipidemia and atherosclerosis. The aim of this study is to detect the correlation between Neuropeptide Y (NPY) SNP rs16147 and its gene expression in chronic kidney disease with and without hypertension. METHODS: This study carried out on 150 subjects who were divided into 3 main groups group (I) 50 CKD patients with hypertension, group (II) 50 CKD patients without hypertension and group (III) 50 healthy individuals. Carotid intima media thickness (CIMT) was measured by Ultrasound. Kidney function test and lipid profile were performed. Genotyping and gene expression of neuropeptide Y (NPY) were performed using real time PCR. RESULTS: There was a significant increase in number and percentage of CC genotype and C allele of NPY SNP distribution in CKD patients with and without hypertension when compared to controls. A significant association was found between CC genotype and C allele and the risk of CKD with hypertension with odd ratio 3.26 and 1.77, respectively. There is a significant positive correlation between NPY gene expression level and CIMT among chronic kidney disease patients with highest level of TC, LDLc and CIMT among CC genotype of NPY gene. CONCLUSION: A significant association was found between CC genotype and C allele of NPY at rs16147 with increase NPY gene expression and risk of developing hypertension in CKD.

The clinical impact of miRNA34a and P53 gene expression in colon cancer.

OBJECTIVE: To study the potential role of miRNA34a gene expression and its relationship with P53 gene expression, fate, stage, metastasis and overall survival of colorectal cancer. PATIENTS AND METHODS: This study was carried out 30 patients with colon adenocarcinoma, 30 patients with benign colon polyp and 30 apparently healthy persons served as controls. All participants were subjected to full history taking, general clinical examination. Complete blood count, liver and kidney function, determination of serum tumor markers were done. Estimation of microRNA 34a and P53 Gene expression by real-time PCR were done. RESULTS: There was a significant negative relationship between serum tumor markers and micro RNA 34a gene expression in cancer patients. Also, there was a statistically significant positive relationship between miRNA34a gene expression and P53 gene expression in both patients groups. The diagnostic accuracy of miRNA34a gene expression was both sensitive and specific for colon cancer. MiRNA34a and P53 gene expression had statistically significant relation with tumor stage and presence of metastases. CONCLUSION: It can be concluded that the level of miRNA34a can be used to differentiate between colon cancers and begin adenomas. MiRNA34a can be used as a prognostic marker in colon cancer.

Association of genetic variants of pentraxin 3 rs3816527 with hypertension in Chronic kidney disease patients.

Hypertension is a nearly constant feature and both a cause and a consequence of chronic kidney disease (CKD). Atherosclerotic lesions showed a marked expression of pentraxin 3 on the surface of lumen and in the plaque. The aim was to assess the correlation of exon 2 of pentraxin 3 gene SNP rs3816527 with hypertension with CKD. The study was conducted on 110 CKD patients (60 patients with and 50 patients without hypertension) and 40 healthy subjects as control. Laboratory investigations including the measurement of fasting blood glucose, lipid profile, and indices of oxidative stress, liver function tests, and renal function tests were done. Genotyping of pentraxin 3 gene SNP rs3816527 was done by real-time PCR. There was a significant difference between CKD patients with hypertension and the subjects in the control group regarding systolic and diastolic BP, urea, creatinine, GFR, TG, cholesterol, LDL, HDL, and total antioxidant levels (p < 0.001). There is a statistically significant difference between CKD patients with hypertension and the other studied groups regarding the frequencies of AA genotype and A allele of exon 2 SNP of pentraxin 3 gene compared to CC genotype and C allele (wild type) (p < 0.001), while there was significant difference between CKD patients without hypertension and control (p > 0.05). Pentraxin 3 AA genotype SNP rs3816527 can be considered as a potential biomarker and a risk factor for CKD patients, especially hypertensive patients, and specifically as an independent predictor of hypertension in CKD.

Serum resistin in acute myocardial infarction patients with and without diabetes mellitus.

AIM: Human resistin is an adipokine, with a possible link to coronary heart disease, and the relationship between serum resistin, insulin resistance, and type 2 diabetes mellitus (T2DM) remains controversial. Therefore, this study assessed serum resistin in patients with acute ST segment elevation myocardial infarction (STEMI), with and without T2DM. METHODS: Between June 2009 and July 2010, 55 subjects were recruited into three groups: 20 non-diabetic patients with acute STEMI (group 1), 20 diabetic patients with acute STEMI (group 2), and 15 healthy controls (group 3). Concentrations of serum lipids, fasting blood glucose (FBG), insulin, troponin I, creatine kinase (CK), lactate dehydrogenase (LDH), and resistin, were estimated. RESULTS: Concentrations of serum total cholesterol, low density lipoprotein cholesterol, FBG, troponin I, CK, LDH, and resistin were significantly higher in group 2 subjects, than in those in groups 1 and 3 (p<0.05). In group 2, serum resistin was positively correlated with serum troponin I and triglycerides (r=0.59, p<0.05, and r=0.47, p<0.05, respectively), but was negatively correlated with high density lipoprotein cholesterol (r=-0.46, p<0.05). However, in this group, serum resistin was not correlated with age, gender, body mass index (BMI), total cholesterol, FBG, insulin, CK, LDH, and the calculated homeostasis model for insulin resistance (HOMA-IR) (p>0.05). Regarding group 1, serum resistin was not correlated to any of these studied parameters (p>0.05). CONCLUSIONS: Serum resistin concentrations are elevated in patients with acute STEMI. This increase is more prominent in patients with T2DM than in those without. However, serum resistin is not correlated with age, gender, BMI, and insulin resistance. These data suggest that serum resistin concentration might be used as a diagnostic biomarker for acute STEMI.