New markers for the detection of polycystic ovary syndrome

Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex genetic disorder of the endocrine system in women. Alterations that occur in women with PCOS can be due to several predisposing factors; among these contributors are genetic and epigenetic variations. Environmental factors play a weaker role, mainly in worsening insulin resistance. Enzyme, protein and genetic markers can depend as a biochemical diagnosis of PCOs. The genetic markers have been identified to be related to PCOS wasn’t useful for early diagnosis, which can only be used to confirm PCOS in patients already exhibiting the definitive symptoms. Protein and enzyme markers are commonly used for prognosis and monitoring the patient to prevent the development of the complications of PCOS. Proteins of the adipose tissue have been found to be greatly related to insulin resistance and the development of PCOS. The nature of enzymes and proteins of instability and easily degradable have prevented sufficient research from being carried out on them. Therefore, the diagnosis of PCOS relies on the analysis of multiple factors

Neutrophil Gelatinase Associated Lipocalin: Is not an Early Marker Inductor for Diabetic Nephropathy in Qatari Population

Background: The WHO Global Report on Diabetes (2016) showed that the number of diabetic patients quadrupled between 1980 and 2016, while causing the death of 1.5 million people. While the global prevalence of diabetes is 9%, the prevalence of diabetes in Qatar is between 17-20%, 45% of which developed diabetic nephropathy. Diabetic Nephropathy is the largest cause of End Stage Renal Disease, and it develops in 20% of diabetic patients. Currently, DN is diagnosed by the detection of microalbumin in urine samples. However, nephropathy can be present even in the absence of albuminuria, and the levels of microalbumin in urine does not correlate with the degree of nephropathic damage. Early detection can prevent total renal failure. Studies have shown that neutrophil gelatinase-associated lipocalin (NGAL) was highly expressed even before the appearance of pathological microalbuminuria in both type 1 and type 2 diabetic patients. The levels of NGAL in urine also correlates with the degree of nephropathic damage. However, currently no information exists about the presence of NGAL in diabetic patients of the Qatari population. Objective: This study aims to determine if there is a relationship between the concentrations of NGAL in urine and kidney function. Methodology: Urine samples of 123 patients were acquired from the Qatar Biobank. Of these, 38 were non-diabetic controls, while 85 were diabetic patients. Type 1 diabetics, pregnant females, smokers, and kidney, liver and cardiovascular disease patients were excluded from the control and case population. Using Enzyme linked immunosorbent assay (ELISA), all samples were tested for the presence of NGAL, and a select few were also tested for microalbumin through an external laboratory. The results obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 24 and Microsoft Excel 2016. Results: No significant difference was found in mean values of uNGAL concentrations in healthy patients, diabetic patients with HbA1c>6% and diabetic patients with HbA1c0.05). However, weak correlation was demonstrated between uNGAL concentrations with serum albumin, HbA1c, serum glucose concentration and albuminuria in diabetic patients with HbA1c>6% (p<0.05). Conclusion: According to the current study uNGAL concentrations does not correlate with any of the kidney function tests, such as glomerular filtration rate, serum creatinine and blood urea nitrogen. So, it cannot be used as a marker to detect diabetic nephropathy in the early stages

Association between Genetic Variants of GC Gene at 4q13.3 and Vitamin D Concentrations in Adult Females

Background: Vitamin D binding protein, encoded by the GC gene (on 4q13.3), plays an important role in transporting vitamin D. Several Genome-Wide Association Studies (GWASs) have established a significant association between variants of GC gene and circulating vitamin D. Objective: This study aims to determine the association of GC gene polymorphisms with vitamin D concentrations in young healthy Arab females. Methodology: 214 female subjects from Qatar University were enrolled in this cross-sectional study. The cut-off value for optimal vitamin D levels was set at 30 ng/mL. The serum vitamin D was measured using ELISA, the genotyping of SNPs (rs2298850, rs3755967, rs2282679, rs7041, rs1155563, and rs17467825) of GC gene was performed by TaqMan assay, and the data was analyzed using SPSS software. Results: The mean age of 214 participants was found to be 21.97 years. Of these, only 182 subjects were included in this study. The data showed that 14.8% were found to have optimal vitamin D levels and 85.2% with suboptimal levels. All studied SNPs were in HWE except SNPs rs7041 and rs1155563. Using the dominant model for rs2298850, the odds ratio to have low vitamin D is 1.48 (p=0.419). Similarly, rs3755967 has a risk of 1.62 (p=0.294); rs2282679 has an odds ratio of 1.32 (p=0.549); and rs17467825 with a risk of 1.48 (p=0.40). The genotypes for vitamin D levels had no significant difference (p>0.05) for all study subjects. Conclusion: The current data showed no significant association between risk alleles of SNPs (rs2298850, rs3755967, rs2282679, rs7041, rs1155563, and rs17467825) with vitamin D levels. Keywords: Vitamin D deficiency; 25-hydroxyvitamin D; GC gene; Vitamin D binding protein; SNPs Abbreviations: 25-hydroxyvitamin D/calcifediol (25-(OH)D); 1, 25-dihydroxyvitamin D/calcitriol (1,25-(OH)2D); Vitamin D Binding Protein (DBP); Group-specific Component (GC); Ultraviolet radiation B(UVB); Vitamin D Receptor (VDR); Retinoid X Receptor (RXR); Parathyroid Hormone (PTH); DNase Hypersensitivity Site (HSIV); Single Nucleotide Polymorphisms (SNP); Chemiluminescent Immunoassay (CLIA); Chemiluminescent- Microparticle Immunoassay (CMIA); Enzyme Linked Immunosorbent Assay (ELISA); High Performance Liquid Chromatography (HPLC); Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS); Body Mass Index (BMI); Overweight and Obese (OWOB); Waist Circumference (WC); Low Density Lipoprotein (LDL); High Density Lipoprotein (HDL); Triglycerides (TG); Interleukin-6 (IL-6); Minor Allele Frequency (MAF); Hardy-Weinberg Equilibrium (HWE); Confidence Intervals (CI); Analysis of Variance (ANOVA

The potential role of vitamin D supplementation as a gut microbiota modifier in healthy individuals

Vitamin D deficiency affects approximately 80% of individuals in some countries and has been linked with gut dysbiosis and inflammation. While the benefits of vitamin D supplementation on the gut microbiota have been studied in patients with chronic diseases, its effects on the microbiota of otherwise healthy individuals is unclear. Moreover, whether effects on the microbiota can explain some of the marked inter-individual variation in responsiveness to vitamin D supplementation is unknown. Here, we administered vitamin D to 80 otherwise healthy vitamin D-deficient women, measuring serum 25(OH) D levels in blood and characterizing their gut microbiota pre- and post- supplementation using 16S rRNA gene sequencing. Vitamin D supplementation significantly increased gut microbial diversity. Specifically, the Bacteroidetes to Firmicutes ratio increased, along with the abundance of the health-promoting probiotic taxa Akkermansia and Bifidobacterium. Significant variations in the two-dominant genera, Bacteroides and Prevotella, indicated a variation in enterotypes following supplementation. Comparing supplementation responders and non-responders we found more pronounced changes in abundance of major phyla in responders, and a significant decrease in Bacteroides acidifaciens in non-responders. Altogether, our study highlights the positive impact of vitamin D supplementation on the gut microbiota and the potential for the microbial gut signature to affect vitamin D response. 2020, The Author(s).Scopu

The role of polymorphisms in vitamin d-related genes in response to vitamin d supplementation

Background. Vitamin D deficiency represents a major healthcare problem. Vitamin D status is influenced by genetic and environmental determinants. Several observational studies have evaluated the association of single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and vitamin D levels. Nevertheless, little is known about the role of these SNPs in the response to vitamin D supplementation. We conducted an interventional study to define the association between SNPs in vitamin D-related genes and the response to vitamin D supplementation in 100 self-reported healthy women of Arab ancestry for the majority. Methods. A total of 100 healthy female subjects received a weekly oral dose of 50,000 IU vitamin D for 12 weeks. Serum vitamin D concentration and metabolic profiles were measured at baseline and 12 weeks post-vitamin D supplementation. The genotypes of 37 SNPs selected from previously reported vitamin D-related genes have been assessed by Fluidigm genotyping assay. Results. Rs731236 (VDR gene) and rs7116978 (CYP2R1 gene) showed a significant association with vitamin D status. The rs731236 GG genotype and the rs7116978 CC genotype were associated with a “vitamin D sufficiency” state. Rs731236 GG and rs7116978 CC genotypes showed a higher response to vitamin D supplementation. Transcription factor binding site prediction analysis showed altered binding sites for transcription factors according to the different rs7116978 alleles. Interestingly, the 37 SNPs previously established to play a role in vitamin D-related pathways explained very little of the response to vitamin D supplementation in our cohort, suggesting the existence of alternative loci whose number and effect size need to be investigated in future studies. Conclusion. In this paper, we present novel data on vitamin D-related SNPs and response to vitamin D supplementation demonstrating the feasibility of applying functional genomic approaches in interventional studies to assess individual-level responses to vitamin D supplementation.This study was supported by funds from Qatar University, Grant ID: QUCP-CHS-17\18-1

Obesity is associated with the upregulation of TLR4 protein but not associated with polymorphisms of TLR4D299G TLR4T399I

Title: Obesity is associated with the upregulation of TLR4 protein but not associated with polymorphisms of TLR4D299G TLR4T399I.Background: Toll-like-receptor 4 (TLR4) is a pathogen-specific receptor, expressed in white blood cells, adipocytes, and other metabolic cells. Lipopolysaccharides (LPS) and free fatty acids (FFA) can act upon TLR4 and activate systematic inflammation that may lead to obesity and metabolic syndrome (MS).Aim: The aim of this research was to investigate the association of TLR4 polymorphisms of TLR4D299G TLR4T399I, with obesity and metabolic syndrome components in young adult female Arab subjects.Methodology: A prospective cross-sectional study was performed on female students from Qatar-University. The subjects were classified according to BMI classifications by WHO category into two groups: "obese; n = 69" and "non-obese; n = 136". Anthropometric measurements included weight (kg), height(m), waist circumference (WC) were assessed, and the body mass index (BMI) was calculated. Several biochemical assays were done to determine glucose and lipid profile. Plasma concentration of Interlukin-10 (IL-10) was measured using ELISA assay. Plasma concentration of IL-6, MCP-1, leptin, and insulin was measured using the multiplex Luminex assay. Also, fresh blood samples were used to measure TLR4 protein expression using flow cytometry assay.Results: TLR4D299G/T399I carriers had no significant association with obesity indicators; body mass index (BMI), body fat percentage (%BF), and waist circumference (WC). Haplotype analysisof TLR4 D299G/T399I showed that GT carriers of TLR4 D299G/T399I had a significant association with increased risk of insulin resistance with (odds ratio = 4.73), 95% CI (1.19- 18.90), (P-value = 0.016). Increased level of leptin was associated with obesity phenotype by BMI, WC, and %BF. In addition, up-regulation of TLR4 protein increased significantly in obese subjects by 1.2 fold over the non-obese, with (P-value = 0.006). Conclusions: TLR4 D299G/T399I polymorphism is associated with increased insulin resistance, a core component of metabolic syndromes but not with obesity. In addition, the up-regulation of TLR4 in obese subjects may be related to insulin resistance with increased leptin suggesting that increased free fatty acids may be a possible link to act as a ligand for TLR4.qscienc