Single Nucleotide Polymorphisms Rs2910164 Research Articles

The Association of miRNA-146a Gene Variation and Multiple Sclerosis in The Iranian Population.

Multiple sclerosis (MS) is a complex human autoimmune-type inflammatory disease of the central nervous system (CNS). MicroRNA-146a (miR-146a) belongs to an endogenous and non-coding RNA family with 18-22 nucleotides long, which modulates the innate and adaptive immune response. Our study aimed to investigate a possible association between rs2910164 and rs2431697 polymorphisms of the miR-146a gene and multiple sclerosis in the Iranian population. A total of 60 MS cases and 100 controls were recruited. Single nucleotide polymorphism (SNP) rs2431697 was genotyped by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SNP rs2910164 was genotyped by using Tetra-primer ARMS-PCR. Statistical Analysis conducted by the chi-squared test utilizing SPSS version 21.0 Software. The Hardy-Weinberg equilibrium assumption was evaluated. The results of the present study suggest the miR-146a gene rs2431697 polymorphism is not associated with multiple sclerosis. However, there is a significant relationship between polymorphism rs2910164 of the miR-146a gene and multiple sclerosis in the population studied (P = 0.012). Our data provide evidence that the miR-146a gene may be involved in creating the susceptibility to MS in the Iranian population.

Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis.

Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA-146a (miR-146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR-146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR-146a, interleukin-6 (IL-6), Toll-like receptor 10 (TLR10), and tumor necrosis factor-alpha (TNFA) genes and the risk for development of advanced-stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR-146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL-6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR-146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR-146a genotype with the IL-6, and stratified miR-146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR-146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk-modifying factors.

Association of <i>CSK, MTHFR, ACE, ADRA2B, TCF7L2</i> gene polymorphisms with dyslipidemia among indigenous and non-indigenous people of Khanty-Mansy Autonomous Okrug – Yugra

The increase in cardiovascular diseases and their complications, diabetes mellitus and metabolic syndrome determines the relevance of early diagnosis and prevention of lipid metabolism disorders by identifying and studying genetic markers of predisposition to dyslipidemia in various populations depending on gender, age and ethnicity.Aim of the study was to investigate the associations of candidate genes CSK, MTHFR, ACE, ADRA2B and TCF7L2 with dyslipidemia in the young indigenous and non-indigenous population living in the Khanty-Mansy autonomous Okrug – Ugra.Material and methods. 863 young people aged 18–44 years were examined, clinical population included nonindigenous and indigenous men and women with metabolic syndrome (n = 344), the comparison group included non-indigenous and indigenous men and women without metabolic syndrome (n = 519). A study of the lipid profile and molecular genetic study was carried out using the polymerase chain reaction method for single nucleotide polymorphisms (SNPs): rs1378942 of the gene CSK, rs1801133 (C677T) of the gene MTHFR, gene ADRA2B, rs7903146 of the gene TCF7L2, rs1799752 of the gene ACE.Results. A high frequency of hypercholesterolemia (79.0 %) and hypertriglyceridemia (65.8 %) was found in the examined men and women. Statistically significant differences were established in the frequency of dyslipidemia in patients with metabolic syndrome by ethnicity and gender (p < 0.001). In the general cohort of men with metabolic syndrome hypercholesterolemia is associated with the TT genotype of SNP rs1801133 (C677T) of the gene MTHFR (p = 0.039), in the women – with the DD genotype of the gene ADRA2B (p = 0.010). In indigenous men of the clinical group an association of hypercholesterolemia with the minor T allele of the gene MTHFR (p = 0.005), of hypertriglyceridemia – with the minor T allele of the gene MTHFR (p = 0.031) and the T allele of the gene TCF7L2 (p = 0.031) was revealed. Among indigenous women of the clinical group hypercholesterolemia is associated with carriage of the minor T allele of the gene CSK (p < 0.001) and hypertriglyceridemia – with the D allele of the gene ADRA2B (p = 0.046).Conclusions. Carriage of minor alleles T of the MTHFR gene and D of the ADRA2B gene is associated with hypercholesterolemia among the examined young people and is statistically significantly higher in the group of patients with metabolic syndrome, as well as among indigenous residents of the KhantyMansiysk Autonomous Okrug – Ugra.

Prospective Functions of miRNA Variants May Predict Breast Cancer Among Saudi Females.

Background Growing knowledge supports the importance of microRNAs (miRNAs) in modulating the initiation and development of breast cancer (BC) and underlying mechanisms. BC is a significant public health in females worldwide, where it remains the leading cause of death among Saudi females. Here, we evaluate the susceptibility of the miRNA genetic variants to the risk of BC in Saudi females. Methods One hundred fifty-four females, including 76 females diagnosed with BC and 78 healthy controls, were analyzed using TaqMan™ (Thermo Fischer Scientific, Waltham, MA) genotyping assays for the miR-196a2 rs11614913 C>T, miR-146a rs2910164 C>G, and miR-499 rs3746444 A>G. We utilized the SNPStats software (https://www.snpstats.net) (Institut Català d'Oncologia, Barcelona, Spain) to choose the best interactive inheritance model for the examined miRNAs. Results The examined miRNA single-nucleotide polymorphisms (SNPs) showed no clear association with the risk of BC (P > 0.05). As for genotypic distributions, significant associations were found for the rs2910164 SNP in most interactive models of inheritance: 2.50 (95% confidence interval{CI}, 1.2-5.17; P = 0.0135) in the codominant model, 2.34 (95% CI, 1.11-4.8; P = 0.0197) in the dominant model, and 2.40 (95% CI, 1.22-4.73; P = 0.0113) in overdominant model. The rs2910164 C/G heterozygosity showed overexpression in cases compared to controls (73.7% versus 53.9%; chi-squared (χ2) = 6.5; P = 0.0109), but the homozygous rs2910164 G/G showed a significant protective effect (21.1% versus 38.5%; χ2 = 17.4; P= 0.019). The heterozygosity did not affect the risk to the BC in the two miRNAs (rs11614913 C>Tand rs3746444 A>G). Conclusion Despite lacking associations with the examined miRNAs, the heterozygous genotype rs2910164 C/Gcan identify at-risk females. More studies should be replicated using a panel of miRNA genes to discover significant associations with the risk of BC.

Association of single nucleotide polymorphism miRNA-146a (rs2910164) with increased predisposition to oral squamous cell carcinoma in central India population.

miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. In the present case-control study, we enrolled 430 subjects from central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC, OR = 2.62; 95% CI: 1.48-4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI =0.21-0.67, p-value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37-0.89, p-value = 0.01). Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings.

Absence of GSTT1 and polymorphisms in GSTP1 and TP53 are associated with the incidence of acne vulgaris.

Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit affecting most teenagers and numerous adults throughout the world. The present study was designed to assess the association of the presence or absence of GSTM1, GSTT1, and single nucleotide polymorphisms rs1695 in GSTP1 and rs1042522 in TP53 gene with acne vulgaris. The cross-sectional case-control study was conducted at the Institute of Zoology from May 2020 to March 2021 and included acne vulgaris patients (N=100) and controls (N=100) enrolled in Dera Ghazi Khan district, Pakistan. Multiplex and tetra-primer amplification refractory mutation system-polymerase chain reactions were applied to investigate the genotype in analyzed genes. The association of rs1695 and rs1042522 with acne vulgaris was studied either individually or in various combinations with GATM1 and T1. A significant association of absence of GSTT1 and mutant genotype at rs1695 (GG) and at rs1042522 (CC) in GSTP1 and TP53, respectively, was found to be associated with acne vulgaris in enrolled subjects. Subjects aged 10-25 years and smokers were more susceptible to acne vulgaris. Our results suggest that genotypes of glutathione S-transferases (GSTs) and TP53 are involved in protection against oxidative stress and may influence disease progression in acne vulgaris.

Association of vitamin D receptor polymorphisms with cardiometabolic conditions in Pakistani population.

Apart from bone related effects, vitamin D has roles in immune modulation, hypertension, diabetes and cardiovascular diseases. Metabolic functions of vitamin D are mediated after binding with vitamin D receptor (VDR). VDR polymorphisms affect its physiological functions. Several VDR single nucleotide polymorphisms (SNPs) were reported previously. However, VDR polymorphisms causing influence on cardiovascular and metabolic disorders have not been investigated in the Pakistani population so far. Therefore, the present study was conducted to evaluate the role of VDR polymorphisms (rs2228570 and rs7975232) in the pathobiology of cardiometabolic disorders. In total, 400 cardiometabolic patients and 226 healthy control human adults were enrolled from Faisalabad, Pakistan. Biochemical parameters (serum glucose, liver function test, renal function test and lipid profile) were analyzed by standard kit methods. Genetic analysis was done by ARMS-PCR assay. Data was analyzed in SPSS v20. Regression analysis revealed that GG and AG genotypes of rs2228570 A>G polymorphism significantly increased the risk of hypertension in cardiovascular patients by 5.29 and 5.94 times respectively (GG: OR=5.29, 95% CI=1.63-17.2, p=0.005; AG: OR=5.94, 95% CI=1.70-20.7, p=0.005). However, rs7975232 C>A polymorphism was not correlated with cardiometabolic conditions. In conclusion, GG and AG genotypes of VDR SNP rs2228570 significantly contribute to hypertension in cardiovascular disease patients.

Identification of SNPs associated with methotrexate treatment outcomes in patients with early rheumatoid arthritis.

Methotrexate is one of the cornerstones of rheumatoid arthritis (RA) therapy. Genetic factors or single nucleotide polymorphisms (SNPs) are responsible for 15%-30% of the variation in drug response. Identification of clinically effective SNP biomarkers for predicting methotrexate (MTX) sensitivity has been a challenge. The aim of this study was to explore the association between the disease related outcome of MTX treatment and 23 SNPs in 8 genes of the MTX pathway, as well as one pro-inflammatory related gene in RA patients naïve to MTX. Categorical outcomes such as Disease Activity Score (DAS)-based European Alliance of Associations for Rheumatology (EULAR) non-response at 4 months, The American College of Rheumatology and EULAR (ACR/EULAR) non-remission at 6months, and failure to sustain MTX monotherapy from 12 to 24months were assessed, together with continuous outcomes of disease activity, joint pain and fatigue. We found that the SNPs rs1801394 in the MTRR gene, rs408626 in DHFR gene, and rs2259571 in AIF-1 gene were significantly associated with disease activity relevant continuous outcomes. Additionally, SNP rs1801133 in the MTHFR gene was identified to be associated with improved fatigue. Moreover, associations with p values at uncorrected significance level were found in SNPs and different categorical outcomes: 1) rs1476413 in the MTHFR gene and rs3784864 in ABCC1 gene are associated with ACR/EULAR non-remission; 2) rs1801133 in the MTHFR gene is associated with EULAR response; 3) rs246240 in the ABCC1 gene, rs2259571 in the AIF-1 gene, rs2274808 in the SLC19A1 gene and rs1476413 in the MTHFR gene are associated with failure to MTX monotherapy after 12-24months. The results suggest that SNPs in genes associated with MTX activity may be used to predict MTX relevant-clinical outcomes in patients with RA.

Qualification and quantification of plasma cell-free DNA after long-term storage conditions in patients with benign prostatic hyperplasia (BPH): a pilot study

Abstract Objectives Free DNA is used as a cancer biomarker due to its low cost, high applicability, and fast, reliable results compared to invasive methods. This study aimed to evaluate the quantification of plasma-free DNA after long-term storage conditions and perform qualification through single nucleotide polymorphism (SNP) screening based on this DNA. Methods Plasma-free DNA samples were quickly isolated from the peripheral blood of both the benign prostatic hyperplasia (BPH) and control group participants and then maintained at −80 °C for four years. Upon thawing, first, free DNA was purified and fluorometric measurements were taken to determine the amount of DNA. Subsequently, the rs6983267, rs12628, and rs1799939 SNPs were screened in the CCAT2, HRAS, and RET genes, respectively. Results Significant results were obtained from the fluorometric measurements in terms of single-stranded DNA (ssDNA) (p<0.001). However, there was no significant difference in SNPs rs6983267, rs12628, and rs1799939 in the BPH group compared to the healthy individuals. Conclusions The data show that fluorometric ssDNA measurements are suitable for quantifying free DNA. The fact that SNP screening can be done successfully in both healthy people and BPH patients suggests that plasma-free DNA can be stored in the laboratory under appropriate conditions.

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer.

Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the susceptibility and severity of this neoplasm in different populations. Eighty-four genetic variants associated with prostate cancer susceptibility were selected from the literature through genome association studies (GWAS). Allele frequencies were obtained from the 1000 Genomes Project, and epidemiological data were obtained from Surveillance, Epidemiology, and End Results (SEER). The PCa incidence, mortality rates, and allele frequencies of variants were evaluated by Pearson’s correlation. Our study demonstrated that 12 SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs6983267, rs11649743, rs2075110, rs114798100, rs855723, and rs2075109) were correlated with epidemiological data in different ethnic groups. Ten SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs11649743, rs2075110, rs114798100, and rs2075109) were positively correlated with the mortality rate. Seven SNPs (rs1048169, rs2961144, rs7000448, rs4430796, rs2066827, rs12500426, and rs114798100) were positively correlated with incidence. Positive correlations of incidence and mortality rates were more frequent in the African population. The genetic variants investigated here are likely to predispose to PCa and could play a role in its progression and aggressiveness. This genetic study demonstrated here is promising for implementing personalized strategies to screen for prostate cancer in diverse populations.

Sequencing of Chromosomal Locus 6q25.1 Revealed Two Significant SNPs rs2046210 and rs2046211 Associated with Breast Cancer: A Case-Control Study in Egyptian Women.

Background:Breast cancer (BC) is one of the major health problems affecting females in Egypt. Certain chromosomal loci abnormalities were proved to be associated with BC in different populations. One of them is chromosomal locus 6q25.1, that affects estrogen receptor gene (ESR) which controls ER receptor expression. Therefore, the aim of this study was to investigate locus 6q25.1 among group of Egyptian female BC patients and compare the results to healthy matched age controls. Methods:Formalin fixed paraffin embedded (FFPE) samples of sixty newly diagnosed BC patients were sequenced for locus 6q25.1 using genetic analyzer with capillary electrophoresis (3500 GA). The identified single nucleotide polymorphisms (SNPs) were compared to blood samples of forty controls. Realtime PCR using TaqMan probes was used for validation. Results:Two SNPs rs2046210 and rs2046211 were significantly associated with BC. Frequency of rs2046210-A minor allele was 30% in controls, while the frequency of rs2046211-G minor allele was 15%. Rs2046210-A allele was associated with increased risk of BC (P=0.0001), while rs2046211-G allele was associated with reduced risk of BC (P=0.021). Combined analysis of both SNPs showed that haplotype A/C was associated with increased risk of BC (P = 0.042). No significant correlation was found between rs2046210-A allele and ER status, while positive association was observed between rs204621-C allele and ER status (p= 0.005). Conclusion:Our data confirmed the important association between locus 6q25.1 and risk of BC in other populations. The frequencies of minor alleles of both significant SNPs will pave the way for a wider large-scale genome study and to be investigated with other BC risk factors.

Examination of the Expression Level HOTAIR, MALAT1and H19 Genes and Single Nucleotide Polymorphisms rs920778, rs619586 and rs2839698 Respectively in the Same Genes, in Response to Treatment of Endometrial Cancer Patients

Examination of the Expression Level HOTAIR, MALAT1and H19 Genes and Single Nucleotide Polymorphisms rs920778, rs619586 and rs2839698 Respectively in the Same Genes, in Response to Treatment of Endometrial Cancer Patients

The prognostic impact of Wilms tumor-1 polymorphism (rs16754) and human myeloid inhibitory C-type lectin-like receptor expression in cytogenetically normal-acute myeloid leukemia

BackgroundThere are several genetic mutations that carry prognostic and predictive values in acute myeloid leukemia (AML). They are also implicated in disease pathogenesis and patient outcome. They can be a target of novel therapies for AML. The aim of the current study was to investigate prognostic value of Wilms’ tumor-1 (WT1) genotypes and human myeloid inhibitory C-type lectin-like (hMICL) receptor expression in normal-cytogenetic group of patients with AML. Genotyping of WT1 mutations was done by Rotor Gene real-time polymerase chain reaction (PCR) while hMICL expression was detected using phycoerythrin (PE)-conjugated mouse monoclonal anti-human (MoAbs) by flow cytometry.ResultsSixty-three patients with cytogenetically normal AML (CN-AML) were included in the study. The alternate allele of WT1 single nucleotide polymorphism (SNP) rs16754 was found in 26.89%. At day 28 of therapy, complete remission was achieved in 100% of cases harboring mutant AG plus GG genotypes but only in 6.38% of cases harboring wild genotype (AA). After 6 months, 88.23% of patients harboring WT1 mutant genotype maintained complete remission, while only 23.40% of patients with wild type showed complete remission. The overall survival in patients harboring mutant WT1 genotypes was significantly longer than in those who carried the wild type gene (P-value, 0.001). Additionally, hMICL was overexpressed in approximately 87.3% of AML cases and inversely related to complete response. Similarly, overall survival was significantly shorter in patients with positive hMICL (P-value, 0.001).ConclusionMutant WT1 genotypes (SNP rs16754) were conversely, associated with complete response, and hMICL overexpression had poor prognostic value in AML.

Drug Transporter ABCB1 SNP Predicts Outcome in Patients with Acute Myeloid Leukemia Treated with Gemtuzumab Ozagamicin: A Report from Children's Oncology Group AAML0531 Trial

Background: Gemtuzumab Ozogamicin (GO), is first ever approved immunotherapy for relapsed AML patients. GO is a humanized anti-CD33 antibody linked with the toxin calicheamicin gamma. Calicheamicin induces DNA damage and cell death once the linked CD33 antibody facilitates its uptake. Previous studies have shown that the drug efflux transporter PgP1, which is encoded by gene ABCB1, influences the cellular accumulation of calicheamicin. PgP1 activity in leukemic cells is also inversely correlated with GO response in patients with AML. Although GO was withdrawn from market due to lack of benefit and increase in early mortality observed in SWOG-S0106 study subsequent multiple randomized studies have shown benefit of GO with significant improvement observed in patients with favorable cytogenetic risk features. In light of these results and recent favorable voting by FDA oncology drug advisory committee based on results of ALFA-0701 trail demonstrating a favorable risk:benefit profile for GO there is increased enthusiasm among AML investigators. Given the potential comeback of GO, it is very timely to focus efforts on identifying genetic biomarkers that can improve our ability to develop personalized treatment with GO. In this study evaluate whether single nucleotide polymorphisms (SNPs) in ABCB1 gene are predictive of GO response in patients with AML.Method: Genomic DNA samples from 942 patients enrolled in the COG trial AAML0531 who gave consent for the study were genotyped for 12 SNPs in the ABCB1 gene . Since AAML0531 was designed to test the benefit of GO in a randomized manner, we analyzed the effect of ABCB1 genotypes on outcomes and risk of relapse (RR) between patients treated with or without addition of GO (GO vs. No-GO respectively).Results: The ABCB1 SNP C3435T (rs1045642) was significantly associated with outcome when analyzed by GO vs. No-GO arm. Presence of C3435T change has been previously associated with lower PgP1 expression. For AML patients in the GO arm, presence of variant allele (CT and TT genotype) was significantly associated with lower risk of relapse (RR) from the end of course 1 (GO vs. No-GO arm: RR: 30 ± 6%, n = 259 vs. 46 ± 7%, n= 235; P < 0.0001) and better 5-year event free survival (EFS) from study than for those in the No-GO arm (GO vs. No-GO arm: 55 ± 6%, n = 340 vs. 45 ± 5%, n= 337; P= 0.006). However, patients with the CC genotype showed no differences in RR (GO and No-GO arms: 45 ± 10%, n = 97 vs. 40 ± 11%, n= 91; P= 0.514) and EFS (GO and No-GO arms: 44 ± 9%, n = 128 vs. 50 ± 9%, n= 132; P= 0.425) between the GO and No-GO arms (Fig 1). Further the rs1045642 genotype was significantly associated with EFS (CC vs. CT/TT: 44 ± 9% vs. 55 ± 6%; P=0.022) and RR (CC vs. CT/TT 45 ± 10% vs. 30 ± 6%, P=0.007) for patients in the GO arm but for those in the No-GO arm no difference in outcome between the genotypes was observed (RR: P=0.278; EFS P=0.466).Conclusion: Our results show that for the nonsynonymous SNP rs1045642 (C>T) in an drug efflux transporter ABCB1, the presence of T allele is associated with better response in patients treated with GO based as compared to standard arm. Since ABCB1 is involved in efflux of calicheamicin the presence of a low expression T allele might result in higher intracellular accumulation of calicheamicin and thus better response in patients treated with GO. [Display omitted] DisclosuresLoken:Hematologics Inc: Employment, Equity Ownership. Walter:ADC Therapeutics: Research Funding; Aptevo Therapeutics: Research Funding.

The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer.

Prostate cancer has a high incidence in men and is the second cause of cancer death among americans male. microRNA (miR) is becoming a potential new prognostic factor for prostate cancer. Single nucleotide polymorphisms (SNPs) are common polymorphisms, characterized by a single exchange of nitrogen based in the DNA. This polymorphism is present in the miRs, altering their function. To evaluate the role of SNP rs1834306 of miR100 and rs2910164 of miR146a in the development and prognosis of prostate cancer. One hundred patients diagnosed with prostate cancer and 68 controls were selected. The identification of SNP was rated by quantitative polymerase chain reaction from blood samples, and the analysis was performed within the presence of SNP and the prognostic variables. In the SNP rs1834306 (miR100), a smaller presence of the polymorphic homozygous genotype was identified in patients with PSA >10 ng/mL, (P=0.03); when evaluating only the presence of the polymorphic allele G (P=0.09) it was compared to the presence of the wild type allele A. Among the patients with prostate cancer, SNP rs2910164 (miR146A), the polymorphic allele was more frequent in patients with a Gleason score ⩾7 than in patients with a Gleason score <7, (P=0.043). In patients with prostate cancer, miR100 was overexpressed in those with pT3 staging compared to pT2 and among those who had biochemical recurrence (P = 0.004 and P = 0.011, respectively). SNP of miR146a acts as a poor prognostic factor (Gleason ⩾7), and the SNP of miR100 is linked to better prognostic data (PSA <10). MiR100 was overexpressed in prostate cancer with worse prognostic factors.

The Prognostic Impact of WT1 Expression Levels, Mutations, and SNP rs16754 in AML Patients: A Retrospective Cohort Study

Background & Objective: The clinical outcomes and treatment options for acute myeloid leukemia (AML) patients are highly dependent upon molecular markers. In this study, Wilms tumor 1 (WT1) (exons 7 and 9) mutations, single-nucleotide polymorphism (SNP) rs16754, and WT1 expression levels in 130 random AML patients were screened; FMs-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), nucleophosmin (NPM1), and CCAAT/enhancer-binding protein alpha (CEBPA) mutations were also evaluated. Materials & Methods: Overall, 130 AML patients were recruited for this study. WT1 mutations were determined by Sanger sequencing, and expression levels were determined by real-time polymerase chain reaction (PCR). The Kaplan-Meier method was used to calculate overall survival (OS) and disease-free survival (DFS). Results: The frequency of WT1 mutations in the study population was 5.4, and it did not affect OS (P=0.98), DFS (P=0.97), or complete remission (CR) rates in AML patients. The major allele of SNP rs16754 in the current study was A. No significant differences were found for OS (P=0.52), DFS (P=0.42), or CR rates among all SNP rs16754 genotypes. The overexpression of WT1 was observed in 83 of patients at diagnosis. No significant difference was found for OS (P=0.84), DFS (P=0.82), or CR rates between AML patients with high and low WT1 expression levels. Conclusion: The results of the current study do not support WT1 mutation, SNP rs16754, or WT1 overexpression at diagnosis, as they were found to be poor prognostic markers in AML patients. © 2021, Zanjan University of Medical Sciences and Health Services. All rights reserved.

Contribution of hsa-miR-146a and hsa-miR-223 gene variations in patients with multiple sclerosis reveals association of rs2910164 and rs1044165 with risk of multiple sclerosis susceptibility

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as...

A duplex probe-directed recombinase amplification assay for detection of single nucleotide polymorphisms on 8q24 associated with prostate cancer.

Single nucleotide polymorphisms (SNPs) have important application value in the research of population genetics, hereditary diseases, tumors, and drug development. Conventional methods for detecting SNPs are typically based on PCR or DNA sequencing, which is time-consuming, costly, and requires complex instrumentation. In this study, we present a duplex probe-directed recombinase amplification (duplex-PDRA) assay that can perform real-time detection of two SNPs (rs6983267 and rs1447295) in four reactions in two tubes at 39°C within 30 min. The sensitivity of duplex-PDRA was 2×103-104 copies per reaction and no cross-reactivity was observed. A total of 382 clinical samples (179 prostate cancer patients and 203 controls) from northern China were collected and tested by duplex-PDRA assay and direct sequencing. The genotyping results were completely identical. In addition, the association analysis of two SNPs with prostate cancer risk and bone metastasis was conducted. We found that the TT genotype of rs6983267 (OR: 0.42; 95%CI: 0.23-0.78; P=0.005) decreased the risk of prostate cancer, while the CA genotype of rs1447295 (OR: 1.89; 95%CI: 1.20-2.96; P=0.005) increased the risk of prostate cancer. However, no association between the two SNPs (rs6983267 and rs1447295) and bone metastasis in prostate cancer was found in this study (P>0.05). In conclusion, the duplex-PDRA assay is an effective method for the simultaneous detection of two SNPs and shows great potential for widespread use in research and clinical settings.

The Risk Stratification of Coronary Vascular Disease as Linked to Homocysteine, its Modulating Genes, Genetic Polymorphisms, Conventional Predictors, and with Antihypertensive Medicaments

Cardiovascular disease (CVD) have multifactorial nature, and owing to their disparate etiological roots, it is difficult to ascertain exact determinants of CVD. In the current study, primary objective was to determine association of single nucleotide polymorphisms (SNP) in folate pathway genes, homocysteine, antihypertensive medication, and of known risk factors in relation to CVD outcomes. The participants numbered 477 (controls, n = 201, ischemic heart disease patients, n = 95, and myocardial infarction cases, n = 181, respectively). SNPs that were queried for homocysteine pathway genes included, "methylene tetrahydrofolate reductase (MTHFR)" gene SNPs rs1801133 and rs1801131, "methyltransferase (MTR)" SNP rs1805087, "paraoxonase 1 (PON1)" SNP rs662, and angiotensin-converting enzyme (ACE) gene polymorphisms rs4646994. Medication data were collected through questionnaire, and serum-based parameters were analyzed through commercial kits. The analysis of variance and multiple comparison scrutiny revealed that age, gender, family history, cholesterol, creatinine, triglyceride, high density lipoproteins (HDL), homocysteine, beta-blocker, ACE inhibitors, MTHFR and PON1 SNPs related to coronary artery disease (CAD). On regression, rs662 SNPs and C-reactive protein had nonsignificant odds ratio, whereas age, gender, creatinine, and HDL were nonsignificant. Family history, cholesterol, homocysteine, beta blocker, and ACE inhibitors, homocysteine, rs1801133 and rs1801131 SNP maintained significance/significant odds for CAD. The current study indicates an intricate relationship between genetic variants, traditional factors, and drug usage in etiogenesis of arterial disease. Differences in SNPs, their modulated effects in consensus with medicinal usage may be related to ailment outcomes affecting coronary vasculature.

Single-nucleotide polymorphisms (SNPs) of antioxidant enzymes SOD2 and GSTP1 genes and SLE risk and severity in an Egyptian pediatric population

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased oxidative stress that participates in immune dysregulation, and injury resulting in loss of immune tolerance and increased auto-antibody production. This study was designed to investigate the effects of genetic polymorphisms of the antioxidant enzymes genes that code for SOD2 (rs2758332) and GSTP1 (rs1695) on SLE risk and severity in Egyptian children and adolescents cohort from Delta region. MethodsThe frequencies of these genes polymorphic variants were compared between 100 SLE children and adolescents and 100 healthy control subjects. Single-nucleotide polymorphisms (SNPs) of the two antioxidants were determined using TaqMan SNP genotyping assay. ResultsIndividuals with the TT and CT genotypes of rs2758332 in the SOD2 gene were of significant risk for SLE patients (OR = 1.831, 95% CI = 1.082–3.101, P = 0.024) and (OR = 1.864, 95% CI = 1.136–3.059, P = 0.014), respectively. Cases who have combined CT + TT genotype were of significant higher risk of SLE (OR = 1.851, 95% CI = 1.156 – 2.962, P = 0.010). While, they did not show any significant association between SOD2 genotypes or alleles with SLE clinical features. In case of the SNP rs1695 in the GSTP1 gene, no significant associations of genotypes or alleles with SLE risk or with SLE clinical features were detected. ConclusionsThis study among Egyptian children and adolescents showed a strong association of the SOD2 rs2758332 not GSTP1 rs1695 polymorphism with the risk of SLE disease.