Association of miR-27a, miR-181a and miR-570 genetic variants with gallbladder cancer susceptibility on North indian population
Ontology highlight
ABSTRACT:
SUBMITTER: Gupta A
PROVIDER: S-EPMC4044931 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:miRNA play role in post transcriptional regulation of genes and serves a range of biological functions such as initiation, development, metastasis etc. which are also hallmarks of cancer. Hence, we evaluated miRNA 181a, miRNA 30c and miRNA 570 in bladder cancer risk association among North Indians. miRNA 570 C/G (rs4143815), miRNA 30c A/G (rs928508) and miRNA 181a C/T (rs12537) single nucleotide polymorphisms (SNPs) were genotyped by allelic discrimination TaqMan assay in 100 bladder cancer (BC) patients and 100 healthy controls. No significant difference was found in the genotype frequencies of the candidate SNPs among cases and controls. However, combined effect of miRNA 570-miRNA 30c (CG + AA) p = 0.005, OR = 0.223, 95% CI and miRNA 570-miRNA 181a (CG + CC) p = 0.003, OR = 0.169, 95% CI conferred association with no risk of BC. miRNA 181a C/T (rs12537), miRNA 30c A/G (rs928508) and miRNA 570 C/G (rs4143815) should be further validated in large sample size to be used as a risk predictor for bladder cancer among North Indians.
| S-EPMC7994493 | biostudies-literature
Project description:Background and aimDefective apoptosis is a hallmark of cancer development and progression. Death receptors (DR4, FAS) and their ligands (TRAIL, FASL) are thought to mediate the major extrinsic apoptotic pathway in the cell. SNPs in these genes may lead to defective apoptosis. Hence, the present study aimed to investigate the association of functional SNPs of DR4 (rs20575, rs20576 and rs6557634), FAS (rs2234767) and FASL (rs763110) with gallbladder cancer (GBC) risk.MethodsThis case-control study included 400 GBC and 246 healthy controls (HC). Genotyping was carried out by Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) to systematically summarize the possible association of SNP with cancer risk. Functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP). False discovery rate (FDR test) was used in multiple comparisons.ResultsThe DR4 C rs20575 A rs20576 A rs6557634, G rs20575 A rs20576 G rs6557634 and G rs20575 C rs20576 G rs6557634 haplotypes conferred two-fold increased risk for GBC. Among these, the DR4 C rs20575 A rs20576 A rs6557634 haplotype emerged as main factor influencing GBC susceptibility as the risk was not modulated by gender or gallstone stratification. Our meta-analysis results showed significant association of DR4 rs6557634 with overall cancer risk, GI cancers as well as in Caucasians. We didn't find any association of FAS and FASL SNPs with GBC susceptibility.ConclusionsThe DR4 haplotype C rs20575 A rs20576 A rs6557634 represents an important factor accounting the patients susceptibility to GBC probably due to decreased apoptosis. However, additional well-designed studies with larger sample size focusing on different ethnicities are required to further validate the results.
| S-EPMC3938657 | biostudies-literature
Project description:BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that negatively regulate target genes. A single nucleotide polymorphism (SNP) in a miRNA sequence may alter miRNA expression and/or maturation, which was proposed to associate with the development and progression of cancer. The rs895819 polymorphism, located in the terminal loop of pre-miR-27a, has been reported to have relevance to several cancers. In this study, we investigated the possibility of association between polymorphism in rs895819 and susceptibility to colorectal cancer (CRC). METHODS: We identified a single SNP, rs895819 in pre-miR-27a, for further investigation, were determined in 205 CRC patients and 455 healthy controls. RESULTS: When taking the AA genotype as a reference, we found that AG genotype was not statistically significantly associated with the risk of CRC (AG vs. AA, OR 1.245, 95% CI: 0.806 - 1.923). However, the GG genotype was significantly associated with risk of CRC (GG vs. AA, OR 1.599, 95% CI: 1.052 - 2.430). In the AG?+?GG vs GG group, no significant difference was detected (OR 1.424, 95% CI, 0.974 - 1.801). GG genotype and G allele was associated with an increased risk of metastasis in this study (P?<?0.001 and P?=?0.003, respectively). CONCLUSIONS: This study found significant association between rs895819 polymorphism in pre-miR-27a and CRC risk. Population-based studies with large number of subjects and long-term follow-up are needed to verify the association of miR-27a polymorphism with CRC susceptibility and severity. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2061490734125077.
| S-EPMC4261532 | biostudies-literature
Project description:Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy.
| S-EPMC4910913 | biostudies-literature
Project description:Studies in European populations have contributed to a better understanding of the genetics of complex diseases, for example, in coeliac disease (CeD), studies of over 23 000 European samples have reported association to the HLA locus and another 39 loci. However, these associations have not been evaluated in detail in other ethnicities. We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background. We therefore performed a validation of European risk loci for CeD in 497 cases and 736 controls of north Indian origin. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region (rs2854275, P=8.2 × 10(-49)). Three loci showed suggestive association (rs4948256, P=9.3 × 10(-7), rs4758538, P=8.6 × 10(-5) and rs17080877, P=2.7 × 10(-5)). We directly replicated five previously reported European variants (P<0.05; mapping to loci harbouring FASLG/TNFSF18, SCHIP1/IL12A, PFKFB3/PRKCQ, ZMIZ1 and ICOSLG). Using a transferability test, we further confirmed association at PFKFB3/PRKCQ (rs2387397, P=2.8 × 10(-4)) and PTPRK/THEMIS (rs55743914, P=3.4 × 10(-4)). The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus (rs9271850, P=3.7 × 10(-23)) and suggested a role of additional four loci. To our knowledge, this is the first replication study of CeD variants in a non-European population.
| S-EPMC4666579 | biostudies-literature
Project description:MicroRNA-27a (miR-27a) is deemed as an oncogene in malignancies including colorectal cancer (CRC), and rs895819 within pre-miR-27a may affect its secondary structure, leading to its aberrant expression and dysfunction of its targeted gene. We investigated genotype and allele frequencies of the locus in 412 I-III stage CRC cases and 412 age- and sex-matched healthy individuals to explore the possible association between them in the north of Chinese population. The results showed that frequencies of alleles A and G and genotypes GG, AG, and AA of the locus were 65.7%, 34.3%, 17.0%, 34.7%, and 48.3% in cases and 69.9%, 30.1%, 9.9%, 40.2%, and 49.8% in controls, respectively. GG genotype of the locus was positively associated with an increased risk of CRC in codominant (P=0.01, adjusted odds ratio =1.541, 95% confidence interval =1.110-2.239 for genotype GG vs AA) and recessive (P=0.003, adjusted odds ratio =1.855, 95% confidence interval =1.221-2.786 for genotype GG vs AA/GA) models, indicating that GG genotype of the locus might increase susceptibility to CRC. Moreover, genotypes AG and GG and allele G were significantly associated with III stage (P<0.001, P<0.001, and P=0.001, respectively), suggesting that the locus was associated with the progression of CRC. These results suggested that rs895819 within pre-miR-27a was involved in colorectal carcinogenesis and progression, genotype GG of the locus might be a susceptible factor for CRC, and allele G and allele G carrier (genotypes AG and GG) could predict CRC progression in north Chinese Han population.
| S-EPMC4621200 | biostudies-literature
Project description:Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India. Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population. Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes. Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs2293889 at TRPS1, rs4148005 at ABCA8, and rs4420638 at APOC1), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels (β = 0.95, SE = 0.16, p < 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B) was associated with 40.62 mg/dL of higher total cholesterol (β = 1.01, SE = 0.23, p < 0.001) and 33.97 mg/dL of higher LDL-C (β = 1.03, SE = 0.19, p < 0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1, and rs660240 at CELSR2). The wGRS derived from five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1, and rs7832643 at PLEC) was associated with 10.64 mg/dL of lower HDL-C (β = -0.87, SE = 0.14, p < 0.001). Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.
| S-EPMC10859749 | biostudies-literature
Project description:Although daunorubicin (DNR) is the most widely used anthracycline to treat acute myeloid leukemia (AML), resistance to this drug remains a critical problem. The aim of this study was to investigate the relationship between AML resistance to daunorubicin and susceptibility to natural killer (NK) cell-mediated cell lysis, and the putative expression of miRs. For this purpose, we used the parental AML cell lines U-937 and KG-1 and their equivalent resistant U937(R) and KG-1(R) cell lines. We demonstrate for the first time that the acquisition of resistance to DNR by the parental cell lines resulted in the acquisition of cross-resistance to NK cell-mediated cytotoxicity. miR microarray analysis revealed that this cross-resistance was associated with miR-181a downregulation and the subsequent regulation of MAP3K10 and MAP2K1 tyrosine kinases and the BCL-2 (BCL-2 and MCL-1) family. Overexpression of miR-181a in AML blasts resulted in the attenuation of their resistance to DNR and to NK-cell-mediated killing. These data point to a determinant role of miR-181a in the sensitization of leukemic resistant cells to DNR and NK cells and suggest that miR-181a may provide a promising option for the treatment of immuno- and chemo-resistant blasts.
| S-EPMC4635878 | biostudies-literature
Project description:Various mutations in microRNAs (miRs) are associated with the pathogenesis of several diseases including cancers and vascular diseases. The present study aimed to investigate the potential association between miR-27a A>G (rs895819) and miR-449b A>G (rs10061133) polymorphisms with the prevalence of type 2 diabetes mellitus (T2DM), and its associated risk factors in the Korean population. Genotype analysis was performed using PCR-restriction fragment length polymorphism analysis to assess the frequency of miR-27a and miR-449b gene polymorphisms in patients diagnosed with T2DM (n=238) and healthy controls (n=247). The miR-27a GG genotype, recessive model, and G allele were significantly associated with a decreased risk of T2DM [adjusted odds ratio (AOR)=0.378, 95% confidence interval (CI): 0.208-0.686, P=0.001; AOR=0.425, 95% CI: 0.246-0.734, P=0.002; AOR=0.640, 95% CI: 0.493-0.831, P=0.001, respectively). Although the miR-449b polymorphism was not associated with the prevalence of T2DM, the genotype and allele combination analyses for miR-27a and miR-449b polymorphisms showed associations with T2DM prevalence. Furthermore, stratification analysis revealed that the miR-27a polymorphism was associated with DM risk factors including body mass index (<28.12 kg/m2, P=0.031), waist circumference (<93.03 cm, P=0.036), systolic blood pressure (<132.67 mmHg, P=0.017), fasting blood glucose levels (<106.26 mg/dl, P=0.015), glycosylated hemoglobin, type A1C (≤125.5 mg/dl, P=0.001), total cholesterol (≤240 mg/dl, P=0.010) and low-density lipoprotein levels (≤130 mg/dl, P=0.028). The present study revealed an association between miR-27a A>G and miR-449b A>G polymorphisms and the risk of DM in Koreans, which suggests that these gene polymorphisms could represent potential markers for predicting T2DM risk.
| S-EPMC8972843 | biostudies-literature
Project description:Genes expression profiling for coronary artery disease (CAD) and its severity were performed in North Indian Population. For CAD a total of 394 differentially expressed genes, of which 331 genes were found to be up-regulated and 63 genes were found to be down-regulated (? 2.0 fold changes, p-value <0.05). The expression analysis for severity of CAD identified 424 genes up-regulated and 97 down-regulated differentially expressed genes in SVD compared to controls, while 239 genes up-regulated and 125 genes down-regulated genes in TVD compared to controls. The microarray data was validated in different cohort with same inclusion criteria using Real-Time PCR. The mean fold mRNA expression levels for genes were calculated. APOA1, CFTR, SRC, ICAM1, ESR1, SHANK2, ITGA1, IFT22, ZGPAT and THBD were selected for this validation which showed similar patterns as found on microarray experiment.
2017-05-06 | GSE98583 | GEO