Background Adams-Oliver syndrome (AOS [MIM 100300]) is a rare, multiple malformation syndrome commonly characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Brain abnormalities and heart defects are also present in most patients. Both autosomal-dominant and autosomal-recessive inheritance of the disease have been observed. To date, six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. Autosomal-recessive mutations are mostly associated with DOCK6 (MIM: 614219) and EOGT (MIM: 615297), while mutations in ARHGAP31 (MIM: 100300), RBPJ (MIM: 614814), NOTCH1 (MIM: 616028), and DLL4 (MIM: 616589) have been linked to autosomal-dominant inheritance. Case We report a case of AOS caused by DOCK6 mutations (c.3190_3191del and c.4491 + 1G > T), showing no signs of scalp ACC or TTLD, but with bilateral ventricular dilation and ophthalmic abnormalities. Results of wholeexome high-throughput sequencing were analyzed using a combination of pathogenicity prediction algorithms, query of variant databases, and review of the literature. Candidate gene variation sites were identified for pedigree verification. Conclusions The correlation between the genotype and phenotype of AOS has great variability, and the specific pathogenesis of AOS remains to be further studied.
Background: Breast cancer (BC) is one of the most common causes of cancer death globally, with a 0.5% increasing incidence per year. Natural killer cells (NK) have a crucial function in immune surveillance mechanisms, which recognize class I human leukocyte antigen (HLA) molecules, expressed on the target cells, through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). Impaired NK cell anti-tumor immunity has particular relevance with BC progression and metastases. KIRs are the most polymorphic receptors of NK cells that modulate NK cell activity against malignant cells through their interactions with their cognate HLA ligands. Materials and methods: Considering this issue, we conducted this study to survey the impact of HLA class I variegation on the susceptibility to the development of BC in Kermanshahi women. In our study, the presence of HLA-C1 and HLAC2 allotypes, HLA-B Bw4 and Bw6 dimorphism, as well as HLA-A Bw4 group, were detected using polymerase chain reaction with sequence-specific primers in 52 patients with breast cancer living in Kermanshah province (Iran) and 40 healthy subjects.Results: Here, we found that the presence of HLA-C1 allotype and HLAC1/HLAC2 genotype was significantly reduced in breast cancer patients compared to the healthy controls (P = 0.041, P = 0.005 respectively). No significant differences were found for HLA-C2, HLA-B Bw4 groups, HLA-B Bw6, and HLA-A Bw4, as well as their genotype.Conclusion: Our results indicated the protective role for HLA-C1allotype and HLAC1/HLAC2 genotype in healthy subjects compared to patients with breast cancer.
Background: Non-small cell lung cancer (NSCLC) is the principal subtype of lung cancer. Among all therapeutic options, platinum-based chemotherapy agents, especially Cisplatin, are still commonly used treatment for NSCLC patients. However, developing chemoresistance in NSCLC cells often gives rise to chemotherapy failure. Therefore, more studies are required to shed light on gene interaction and cellular pathways involved in initiating and developing resistance to platinum-based chemotherapy in NSCLC. Hence, it is urgent to find the key genes, microRNA (miRNAs), and potential molecular mechanisms implicated in chemoresistance and present markers to predict response to platinum-based chemotherapy in NSCLC patients. Methods: The microarray datasets GSE6410, GSE7035, GSE14814, GSE26704, GSE73302 were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using R software. Functional and pathway enrichment analyses were performed using the Enrich R site. Then, the protein-protein interaction (PPI) network and hub genes were obtained using the Cytoscape software. Further, the miRSystem database was performed to predict the miRNAs regulating the hub genes. Moreover, Cytoscape software and the CytoHubba plugin were used to construct the miRNA-target interaction network and hub modules. Finally, the Kaplan-Meier curve was used to demonstrate the survival curves and assess the association of the genes signature with clinical outcomes. Results: A total of 142 differentially expressed genes (DEGs) were found. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses present the p53 signaling pathway as the most significant pathway. Besides, from the top ten terms obtained of Biological Process, Molecular Function, and Cellular Component, the first ones, including cholesterol biosynthetic process, the extrinsic component of external side of plasma membrane, cytokine activity, were selected respectively. Based on the PPI network, the ten nodes with the highest degree were screened as hub genes. In addition, from the miRNA-target regulatory network in Cytoscape, ten hub nodes were found. Ultimately, according to Kaplan-Meier curve, BTG2 and TP53I3 with p-value <0.05 were associated with a better prognosis. Conclusions: In the present study, DEGs, candidate miRNAs, and underlying mechanisms involved in chemoresistance were identified to suggest potential biomarkers to provide new clues for the prediction of response to platinum-based chemotherapy.
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease that leads to axon demyelination and white matter plaque formation. The aim of the present study is to inspect the association between single nucleotide polymorphisms (SNPs) of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) and MS predisposition. The genotyping of the three genetic variants was conducted through tetra-plex-based real-time polymerase chain reaction (T-plex RT-PCR) method combined with the SYBR green fluorescent dye. Sixty-eight Iraqi MS patients and fifty healthy individuals (controls) were enrolled, and their DNA was extracted from whole blood. The optimum annealing/extension temperature was set at 58 degrees C. For each SNP, allele-specific fragments were identified by their melting points generated through real-time PCR. Agarose gel electrophoresis was performed to confirm the results. The distribution of the IL4 SNP genotypes in patients and controls was in good agreement with Hardy-Weinberg equilibrium, while there was a skewness from Hardy-Weinberg equilibrium in patients' group for both IL17A and IL33 SNPs. Multinomial logistic regression analysis was performed to investigate the association between the studied variants under four genetic models (dominant, recessive, over-dominant, and co-dominant) and MS risk. However, there were no significant differences in genotype/allele frequencies of three SNPs between patients and controls. Taken together, our study indicated that genotype/allele of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) SNPs may not play a considerable role in the predisposition to MS in this sample of the Iraqi population. However, SYBR green-dependent T-plex RT-PCR can be a cost-effective, reproducible and simple method for genotyping SNPs of interest.
Background: Proprotein convertase subtilisin/kexin type 9, a member of the serine protease family, plays an important role in the regulation of plasma low density lipoprotein cholesterol by stimulating the degradation of LDL receptor. Method: In this meta-analysis, we explored the correlation of PCSK9 polymorphisms E670G and D374Y with the elevated plasma lipid levels, which leads to a condition known as hypercholesterolemia, by calculating the standardized mean difference and Odds Ratio with 95% confidence interval. The statistical analysis was done using SPSS version. Results: Under dominant genetic model, pooled results had shown that PCSK9 E670G polymorphism was associated with higher LDL-C levels among the Asians (SMD = 0.53; I-2 = 40%; OR = 0.7610; 95% CI = 0.6554 to 0.8837 and p value = 0.003). Conclusion: The close relationship between both polymorphisms of PCSK9 gene i.e. E670G and D374Y, with the elevated plasma LDL-C levels has been observed. E670G polymorphism is highly prevalent among the Asian population.
Objective: Various reports have examined the contribution of the CTLA4 c.49A > G (rs231775; p.Thr17Ala) gene variant with different cancerous disorders. This meta-analysis was executed to further probe into the involvement of this missense variant with the susceptibility for hepatocellular carcinoma (HCC) and gastric cancer (GC). Methodology: Following a wide-based scrutinized search of the internet done by three independent researchers for the contribution of the CTLA4 c.49A > G (rs231775; p.Thr17Ala) variant with the cancer risk up to February 2021, only 16 case-control studies were found relevant and usable to the analysis out of 575 total retrieved reports. Multiple genetic models were checked for the proposed association through the computation of the odds ratio (OR) in addition to their 95% confidence intervals (95%CIs). Stratification and regression analysis was also carried out for the analyzed reports based on their geographical distributions, genotyping techniques, source of cancer-free controls, genetic equilibrium within cancer-free controls, and quality score. In addition, trial sequential analysis (TSA) was applied to test for the adequacy of the total sample size. Results: This meta-analysis has included 4320 HCC and GC patients in conjunction with 6601 cancer-free controls. This work disclosed a significant association for the CTLA4 c.49A > G (rs231775; p.Thr17Ala) variant with HCC among overall subjects tested by the recessive model [OR = 1.235, 95% CI = 1.050-1.453, P-value = 0.011]. Similarly, an elevated risk of GC was noticed associated with this variant within the overall subjects tested by the allelic model [OR = 1.225, 95% CI = 1.070-1.401, P-value = 0.003], and dominant model [OR = 1.352, 95% CI = 1.081-1.691, P-value = 0.008]. Furthermore, the stratification analysis showed a verification of correlation for this variant with HCC in Asian subjects under the recessive model, while the association was observed to be significant with GC in Asian and Caucasian patients under the dominant model. TSA confirmed that this work had significant findings noting that the collective Z-curve spanned the examining borderlines prior to attaining sample size confirming the acceptability of the study sample size. Conclusion: The CTLA4 c.49A > G (rs231775; p.Thr17Ala) gene variant could be considered as an actual risk factor for the susceptibility of HCC and GC warranting efficient and adequate genetic counseling for this gene variant carriers.
Diabetic nephropathy (DN) was considered as the major cause of end-stage renal disease (ESRD) with the high mortality rate in the affected patients. Patients with DN are at high risk of death from cardiovascular diseases. C-reactive protein (CRP) gene has been known to be effective in the pathogenesis of renal and cardiovascular disease. The aim of the present study was to investigate the association between two CRP polymorphisms, rs2794521 and rs1800947, and risk of DN. Seventy-five patients with DN, fifty patients with diabetic mellitus and fifty healthy controls were enrolled. The genotyping of rs2794521 and rs1800947 were done by using PCR-RFLP. The analysis of the results indicated that rs2794521 was significantly associated with susceptibility to DN but no diabetic mellitus. No association was observed between rs1800947 and the DN risk. The obtained data suggested that rs2794521 may play a role in the etiology of DN.
Helicobacter pylori (H.pylori) is the main reason for gastric disorders including gastric lymphoma, ulcer disease, gastric carcinoma (GC), and chronic atrophic gastritis. H.pylori has two more significant virulence factors named cagA and vacA. Some host cytokines polymorphisms (Interleukin (IL-1) and tumor necrosis factor (TNF-alpha)) may contribute to H. pylori-related diseases. In the present study, we investigated the association of H. pylori gastritis and its pathogenic genes as well as the association of IL-1 ss and TNF- alpha polymorphisms in patients with gastritis. We collected gastric biopsy samples from patients with gastritis. After extracting DNA from biopsy specimens infected with H. pylori, cagA + and vacA + were detected by the polymerase chain reaction (PCR). To genotyping TNF- alpha polymorphism at position 308 and IL-1 ss polymorphism at position 511, PCR-based restriction fragment length polymorphism analysis was performed. Our study indicated that IL-1 ss-511 polymorphism, unlike TNF-alpha-308 polymorphism (P = 0.030), did not show a significant relationship between patients infected with H. pylori (p = 0.219). Also, our results indicated that alleles C and T of polymorphism of IL-1 ss-511 and alleles G of TNF alpha-308 were not significantly correlated with cagA status among patients infected with H. pylori (p = 0.793, p = 0.674, p = 0.179, respectively) unlike allele A of TNF alpha- 308 (p = 0.016).
Our research focused on the development of a regulatory network of miRNA-lncRNA and miRNA-transcription factor associated with Breast Cancer (BC) and Ovarian Cancer (OC), utilising experimentally identified data from previous research works. The regulatory data from the target network helped in the identification of the most vital miRNA, lncRNA and transcription factor (TFs) hub molecules involved in the prognosis of BC and OC. Breast cancer is one of the leading types of cancer in the world whereas ovarian cancer is difficult to detect due to the lack of symptoms in the initial stages. lncRNAs are known to compete for miRNAs as per previous evidence shown in favour of the competing endogenous RNA theory. TFs are vital proteins that regulate the expression of protein coding genes. miRNAs have been known to be involved in post-transcriptional gene silencing. Thus miRNA-lncRNA interactions and miRNA-TF interactions should have a significant impact on the expression of different genes, the irregularity of which leads to diseases like cancer. Our work has revealed three lncRNAs: KCNQ1OT1, XIST and NEAT1 as well as two TFs: RELA and TP53 to have the most significant impact on both breast and ovarian cancer. We identified four miRNAs which had the maximum lncRNA targets, common to both cancers: hsa-mir-93-5p, hsa-mir-519d-3p, hsa-mir-106a-5p and hsa-mir-106b-5p. The top 15 miRNAs having maximum TF targets were found to be identical for both cancers.
Background: SARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease. Aim: We aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI. Subjects and methods: A case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique. Results: Lymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, codominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, chi(2) = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030). Conclusion: Single nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.
Purpose: The present study was aimed to investigate the association of Bisphenol-A (BPA) and MDM2 SNP309 polymorphism with the risk of breast cancer in Indian women. Methods: Blood samples from breast cancer patients and healthy controls were analyzed by using UV visible spectrophotometry for structural changes in blood components by BPAQ. MDM2 SNP309 polymorphism was investigated by using TETRA ARMS-PCR. Results: On comparing control groups, there is an increased mean absorbance at a range of 250 nm to 300 nm and 360 nm to 450 nm in breast cancer patients. The allele frequencies of case subjects (T, 0.47; G, 0.53) were significantly different from those of control subjects (T, 0.66; G, 0.34) (p = 0.011). The proportion of GG genotype of the SNP309 in breast cancer patients (28.88%) was significantly higher than that of control groups (13.33%). With TT genotype as reference, the genotypes (TG + GG) containing G allele as dominant form in breast cancer patients (OR, 2.80; 95% CI, 1.12-7.00); p = 0.025) were significantly associated with breast cancer. Conclusions: The results revealed that there is an association between active metabolite of Bisphenol-A and MDM2 SNP309 G variant with the risk of breast cancer in Indian population.
Spinal Solitary Fibrous Tumour is a rare soft tissue neoplasm. Although a lot of genes are involved in Spinal Solitary Fibrous Tumour progression, survival and metastasis, NGFI-A binding protein 2 (NAB2) - signal transducer and activator of transcription 6 (STAT6) gene fusion is one of the most commonly occurring genetic abnormalities in all types of Solitary Fibrous Tumours (SFT). The interaction of STAT6 (Early Growth Response (EGR) transcriptional activator) and NAB2 (EGR transcriptional repressor) activates the conversion of the transcription repressor to the transcriptional activator and promotes EGR-induced promoter activity. EGR has shown to plays a role in the regulation of cell survival, proliferation and cell death. Cis-regulatory elements (CREs) are genomic sequences in non-coding regions of the genomic DNA which binds with the transcription factors, and they play an essential role in precise control of gene expression. CREs composed of enhancers, suppressors and insulators play pivotal roles in gene expression throughout life and development. They have important role in maintaining the normal homeostasis, preventing organogenesis, tumourigenesis and teratoma formation. In this study, we investigate the non-coding regions in the human genome to detect enhancers and suppressors present in different tissue samples of Spinal SFT using Encyclopedia of DNA Elements (ENCODE). The study of these enhancers and suppressors may be used to develop newer diagnostic and treatment strategies. A total of 75 genes and immunohistochemistry (IHC) markers expressed in Spinal SFT were obtained from PubMed and Google Scholar. CREs were identified using the ENCODE consortium. Protein interaction network was obtained using String v11.0 using the proteins corresponding to these 75 genes. Results obtained from ENCODE were enumerated and web-hosted for public access to design a treatment strategy. This may enable the wet lab scientist design CREs specific for Spinal SFT using the in silico results obtained.
Background: Ovarian cancer (OCa) is the most lethal gynecologic cancer in women. Genes involved in the synthesis of estrogen and its polymorphisms might have an influence on OCa. The current study aimed to examine the association of selected polymorphisms of CYP17A1, CYP19A1, and HSD17B1 genes in the South Indian population with OCa. We examined single nucleotide polymorphisms (SNPs) in the CYP17A1 (rs743572), CYP19A1 (rs10046), and HSD17B1 (rs605059) genes in South Indian women with OCa (n = 200) and agematched controls (n = 200). Methods: All samples were genotyped using TaqMan allelic discrimination assay for all three polymorphisms. Results: The study revealed significant increase of CC genotype (OR = 3.93; 95%CI = 1.86-8.28; p <= 0.001) and C allele frequency (OR = 1.68; 95%CI = 1.25-2.26; p <= 0.001) of rs743572 polymorphism, and CT genotype (OR = 1.61; 95%CI =1.06-2.43; p = 0.023) and T allele frequency (OR = 1.46; 95%CI =1.07-1.98; p = 0.015) of rs10046 polymorphism in OCa patients in comparison with controls. Furthermore, for rs743572 polymorphism, dominant and recessive models and the dominant model of the rs10046 polymorphism revealed a significant association with OCa risk. Additionally, the rs743572, and rs10046 polymorphisms were associated with clinical characteristics of OCa. Conclusion: The results of the current study indicated an association between CYP17A1 and CYP19A1 gene polymorphisms and the progression of OCa and the HSD17B1 gene polymorphism did not show any association with OCa risk. However, studies on different populations with a larger number of sample sizes are needed to support the conclusions.
Antisense non-coding RNA at the INK4 locus (ANRIL) is a long non-coding transcript localized within, and antisense to, the genes encoding the cyclin-dependent kinase inhibitor-2A/B (CDKN2A/B) on chromosome 9p21. Recent evidence implicates the CDKN2A/B locus as a causal candidate for developing type 2 diabetes mellitus (T2D). However, aggregate published information to date regarding the specifics of the statistical association between T2D and the genetic variants in the ANRIL region of the CDKN2A/B locus remains equivocal and ambiguous. To clarify this discrepancy, we performed a meta-analysis based on the genotype prevalence and allele frequency of the rs564398 polymorphism (T > C) in ANRIL gene in multiple ethnic populations. The main goal of this work was to conduct a systematic review with a meta-analysis of published data between 2007 and 2018 to determine whether the rs564398 polymorphism of ANRIL gene plays a potential role in predisposition to T2D, also to evaluate the strength, accuracy, and features of this association. We have systematically reviewed studies from databases published between 1990 and 2021. A total of 202 articles were collected, of which only 13 studies from 9 articles (including 13,510 cases and 18,231 controls) met the inclusion criteria and were selected for the statistical meta-analysis. In the present meta-analysis, we have investigated the potential associations between the selected SNP rs564398 and the predisposition to develop T2D, by conducting replicated analysis of already analyzed studies looked for this association, and expand our results by adding new articles published after 2012 and have not been reviewed in a previous meta-analysis, to form our own conclusion about the nature of this association. In contrast to other studies of the locus, we emphasized the differences of risk alleles and genotype influence among different ethnic groups. Ourmeta-analysis indicated that rs564398 [(OR 1.01, 95% CI [0.92, 1.12], P = 0.79) in the dominant model/ [(OR 1.03, 95% CI [0.91, 1.17], P = 0.64) in the recessive model/[(OR 1.00, 95% CI [0.91, 1.09], P = 0.93) in the additive (TC Vs. TT) model]/[(OR 1.00, 95% CI [0.92, 1.08], P = 0.96) in the additive (TC Vs. CC) model]/[(OR 1.02, 95% CI [0.94, 1.11], P = 0.61) in the allelic (C Vs. T) model] is not associated with the development of T2D overall. However, results also revealed slight association in some populations of the included studies. Although our results indicated a lack of association, more extensive studies with larger sample sizes and mixed ethnic groups are necessary to provide a more reliable estimation to confirm the association between rs564398 and T2D. Defining a putative molecular mechanism of rs564398 influence in the pathophysiology of T2D appears warranted.
Breast cancer represents the leading cause of cancer-related death in women globally. Obesity is one of the risk factors for breast cancer, particularly in postmenopausal women. Adiposopathy causes hypertrophy, which promotes metabolic dysregulation, hypoxia, inflammation, insulin resistance, and altered adipokine production such as vaspin and omentin-1. The objective of this study is to inspect the link between the vaspin rs2236242 and the Val109Asp omentin gene polymorphisms and their serum levels with breast cancer occurrence in postmenopausal females. The gene polymorphisms of vaspin rs2236242 and Val109Asp omentin were identified by T-ARMS-PCR and PCR-RFLP respectively. The glucose homeostasis traits, lipid profile, total antioxidant capacity, and circulating vaspin and omentin-1 levels were all assessed. The AT genotype of vaspin rs2236242 and the Val/ Asp genotype of Val109Asp omentin were more prominent in breast cancer patients than the TT and Asp/Asp genotypes respectively. Breast cancer patients showed significant lower levels of serum vaspin and omentin-1. The AT genotype of the vaspin rs2236242 polymorphism, the heterozygous Asp/Val genotype of the omentin1 gene, and low serum vaspin and omentin-1 levels are more associated with breast cancer incidence. On the flip side, higher levels of serum vaspin and omentin appear to protect against the incidence of breast cancer.
Introduction: Polycystic ovary syndrome (PCOS) affects 4-20% of women of reproductive age. The contribution of genetic factors to the etiology of PCOS is 79%, and the contribution of the environment, lifestyle and individual history is 21%. It is believed that the increased production of androgens in PCOS is a consequence of dysregulation of various genes involved in the synthesis of steroid hormones, such as CYP11 , CYP17 and CYP19. Conflicting data on the association of the CYP17 gene polymorphism (rs743572) with PCOS determined the purpose of this meta-analysis -to study this association in a larger general population in order to determine whether polymorphism in the CYP17 T/C promoter is associated with an increased risk of PCOS. Methods: A systematic search was carried out in various databases for articles on the relationship between rs743572 polymorphism of gene CYP17 and PCOS risk published up to May 2021. The articles were analyzed in accordance with the recommendations for systematic reviews and meta-analyzes (PRISMA). The criteria for inclusion of studies in the meta-analysis were: (i) case-control studies with healthy populations as controls; (ii) a study describing the diagnostic criteria for PCOS, sources of cases and controls; (iii) studies of genetic associations showing the frequency of genotypes of the studied polymorphism and PCOS in humans; (iv) sufficient genotype data to calculate odds ratio (OR) and 95% confidence interval (CI). The control HWE was first assessed for each study using the chi-square test (chi 2). Meta-analysis was performed using Review Manager version 5.4. Odds ratios (OR) with a 95% confidence interval (CI) were used to assess the strength of the association between the rs743572 polymorphism of gene CYP17 and PCOS. Pooled OR was calculated for dominant (CC + TC vs. TT), recessive (CC vs. TC + TT), and allelic (C vs. T) models, as well as for homozygous (CC vs. TT) and heterozygous (TC vs. TT) models. Results: Out of 577 potentially relevant articles, 17 articles were selected for eligibility assessment after excluding irrelevant and duplicate articles. 2283 cases and 2200 controls were evaluated to identify the relationship between the rs743572 polymorphism of the CYP17 gene and PCOS. Carriage of allele C was considered to increase the risk of PCOS. A significant association with PCOS risk was found for rs743572 in the general population using dominant, allelic and heterozygous models: (p = 0.005, OR = 1.41, 95% CI 1.11-1.79; p = 0, 006, OR = 1.28, 95% CI 1.07-1.53; p = 0.01, OR = 1.38, 95% CI 1.07-1.77), respectively. An association between this polymorphism and PCOS risk was not found in the recessive and homozygous models: (p = 0.16, OR = 1.21, 95% CI 0.93-1.58; p = 0, 08, OR = 1.31, 95% CI 0.96-1.78), respectively. Subgroup analysis according to the ethnicity of the participants showed significant associations between Asian and European populations: a higher association was found among Asian populations in the dominant model (p = 0.04, OR = 1.59, 95% CI 1.02-2.48). Conclusions: The meta-analysis showed an increased risk of PCOS in carriers of the C allele rs743572 , thus, polymorphism rs743572 is a risk factor for PCOS, especially in the Asian population. To determine the genetic risks of PCOS, further research is needed on different haplotypes and their association with PCOS risk.
Researchers have consistently linked some TCF7L2 gene variations, such as rs7903146, rs12255372, and rs11255372, to Type 2 diabetes mellitus (T2DM) in numerous populations and ethnic groups. The goal of this study is to show if the TCF7L2 variations rs4506565 T/A is linked to T2DM in Iraqi Arab patients. For this purpose, a case-control study was conducted with 100 T2DM patients and 100 controls. The Tetra-Primer ARMS-PCR Technique was used to genotype TCF7L2 rs4506565 T/A, making use of newly-designed primers. The study concluded that the TCF7L2 gene polymorphism rs4506565 T/A shows no significant difference in genotypes in any of the codominant, dominant, over dominant, recessive, and additive models. The dominant model has a significance with age but no significance with other parameters.
Background: Vitiligo is a complicated disorder identified by advanced degeneration and loss of melanocytes. Some of the main factors that cause vitiligo are cytotoxicity, autoimmunity, along with several genetic factors. Aim: The current study aims at evaluating the association of TNFAIP3 rs6920220 and DEFB1 rs1800972 gene polymorphisms as risk factors of non-segmental vitiligo in Egyptian patients. Patients and methods: This study was conducted on 125 patients with non-segmental vitiligo and 110 age and gender-matched healthy controls. Genotyping of TNFAIP3 rs6920220 and DEFB1 rs1800972 polymorphisms were analyzed by TaqMan probe-based real-time PCR. Results: Significant differences in the genotypes and alleles distributions of both polymorphisms were detected between patients and controls. The AA and GA genotypes of TNFAIP3 rs6920220 increase the risk of vitiligo with OR 4.422 and 1.863 respectively. The (GA + AA) model reported risk with OR 2.016 compared to the GG genotype. The CG, GG genotypes compared to the CC genotype of DEFB1 rs1800972 were found to have an increased risk of vitiligo with OR1.7 and 2.865 respectively. The (GG+ CG) model had OR 1.856. The AA genotype, the A allele of TNFAIP3 rs6920220, the GG genotype, and the G allele of DEFB1 rs1800972 were more frequent in patients with the progressive course and those with a positive family history of other autoimmune diseases as compared to controls. Conclusion: TNFAIP3 rs6920220 and DEFB1 rs1800972 polymorphisms could participate in the pathogenesis of vitiligo and might be considered as potential risk factors for vitiligo.
Physical exercise induces important system disturbances in the human body in a dose-response manner. Meta-analyses of genome-wide expression studies (GWES) might contribute to identify gene expression patterns and to a better understanding of the molecular mechanisms behind the complexity of adaptations to exercise, under a systems biology approach. Here, we aimed to analyze available data for human GWES that have evaluated the effect of exhaustive exercise in peripheral blood mononuclear cells (PBMC) and white blood cells (WBC). Three primary datasets retrieved from the NCBI Gene Expression Omnibus were meta-analyzed using a random effects model in the NetworkAnalyst software. After identifying nine differentially expressed genes (DEGs), we performed functional enrichment analyses to extract relevant biological information. A protein-protein interactions network on DEGs was built to evaluate the associated regulatory pathways. We found that five upregulated genes were members of the heat shock protein family, one of the top stress-response groups of genes. The enrichment analysis revealed key roles of the DEGs on the cellular adaptations to exercise-induced stress (i.e., temperature stimulus, topologically-incorrect and unfolded proteins). Our comparison analysis of DEG signatures found in blood cells with the expression pattern on muscle skeletal tissue showed some common genes. Thus, novel DEGs that might serve as hormetic mediators to exercise-induced adaptations were identified. Further experimental research is needed to validate these findings.
Nephrotic syndrome (NS) remains the most frequent indication of glomerular disease in childhood. The NPHS1 gene encoding nephrin protein is one of the common mutant genes in SRNS (Steroid Resistant Nephrotic syndrome) patients. These gene mutations are more likely to progress into ESKD (end-stage kidney disease). In the present study, we investigated the pathogenesis of the NPHS1 gene in Indian patients with SSNS and SRNS. Ninety-six children have been involved in the present study in which 37 belong to Steroid Sensitive Nephrotic syndrome (SSNS), 27 belong to Steroid Resistant Nephrotic syndrome (SRNS) 32 are healthy individuals. We designed a panel of NPHS1 gene (CDS- Coding sequence) and performed Illumina sequencing (MiSeq). We found a total of 45 variants in the NPHS1 gene. In addition, we found novel pathogenic c.2441A > G and two likely pathogenic missense variants, p.Gly395Ser, p.Ser400Pro in SSNS and SRNS patients by ACMG criteria. Therefore, early diagnosis of steroid resistant nephrotic syndrome in the Indian population can be made by identifying genetic variants using a customized gene panel.
