MGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer.
Ontology highlight
ABSTRACT: Background
Metabolite genome-wide association studies (mGWAS) are key for understanding the genetic regulation of metabolites in complex diseases including cancers. Although mGWAS has revealed hundreds of metabolomics quantitative trait loci (mQTLs) in the general population, data relating to gastric cancer (GC) are still incomplete.Methods
We identified mQTLs associated with GC by analyzing genome-wide and metabolome-wide datasets generated from 233 GC patients and 233 healthy controls.Results
Twenty-two metabolites were statistically different between GC cases and healthy controls, and all of them were associated with the risk of gastric cancer. mGWAS analyses further revealed that 9 single nucleotide polymorphisms (SNPs) were significantly associated with 3 metabolites. Of these 9 SNPs, 6 loci were never reported in the previous mGWAS studies. Surprisingly, 4 of 9 SNPs were significantly enriched in genes involved in the T cell receptor signaling pathway.Conclusions
Our study unveiled several novel GC metabolite and genetic biomarkers, which may be implicated in the prevention and diagnosis of gastric cancer.
SUBMITTER: Yang S
PROVIDER: S-EPMC8474935 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCytotoxic T protein lymphocyte antigen-4 (CTLA-4) plays a key role in regulating the T-cell system, where occurrence of disturbances in the system seen by imbalances in Th1 and Th2 levels is believed to be one of the etiologies of schizophrenia. Single-nucleotide polymorphisms (SNPs) at rs5742909 in the CTLA-4 gene (C→T) might affect the expression level of CTLA-4 protein.Aims and objectivesThe aim of this study was to determine the genotype distribution of the CTLA-4 gene (rs5742909) in patients with schizophrenia at Rumah Sakit Jiwa Prof. Dr. Soerojo Magelang and identify the correlation of these genetic polymorphisms as the risk factors of schizophrenia.Materials and methodsThis research was conducted through the stage of submitting ethical approval, primer design, chromosomal DNA isolation, optimization of polymerase chain reaction conditions, and data analysis.ResultsBased on the results of the study, the CC genotype was shown in 36 patients (78.26%), TT genotype in 10 patients (21.73%), and no TT genotypes. However, statistical analysis using Fisher's exact and binary logistic regression statistical test showed no significant relationship between genetic polymorphism of the CTLA-4 rs5742909 against risk factors for schizophrenia (P = 0.05; α = 5%).ConclusionSNP at rs5742909, C-to-T-allele transition, was not significant associated with the risk of schizophrenia.
| S-EPMC7020830 | biostudies-literature
Project description:Although LGALS3 has been widely studied, the genotypes of the LGALS3 single nucleotide polymorphism (SNP) loci in skull base chordoma (SBC) have been not well defined. The aim of the current study was to analyze two LGALS3 SNP genotypes in patients with SBC. A total of 48 patients with SBC who underwent surgical treatment in Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University (Beijing, China) and 66 healthy participants were included in the present study. A total of two SNPs (LGALS3+191 C>A and LGALS3 +292 A>C) were selected for sequencing analysis of amplified target fragments from DNA that was extracted from blood samples. The clinical features of the patients were recorded, follow-up was conducted and statistical analysis was performed with SPSS 20.0. There were no differences in age and sex between the patients and control group. In addition, there were no significant differences in the distribution of genotypes (P=0.662) and allelic frequencies (P=0.638) at LGALS3+191 C>A between the two groups. However, significant difference was observed in the allelic distributions at LGALS3 +292 A>C between them (P=0.016), and allele A was associated with the occurrence of SBC. The distribution of the genotypes at LGALS3 +292 A>C was not significantly different in the additive model (CC vs. AC vs. AA, P=0.083) but was significantly different in the dominant model (CC+AC vs. AA, P=0.043). In the Kaplan-Meier analysis, there were no significant differences in the overall survival and progression analysis between different genotypes at LGALS3 +191 C>A (P=0.168 and P=0.120) in patients with SBC. There was no significant difference in overall survival was observed between the genotypes at +292 A>C (P=0.595). However, the progression-free survival (PFS) time of the CC+AC genotype group was longer compared with the AA genotype group (P<0.001). In the univariate and multivariate analysis of tumor progression, PFS was shorter in the AA genotype group compared with the CC+AC genotype group (P<0.001). The allele A and AA genotype at LGALS3 +292 A>C were observed to be associated with a higher risk of SBC, and the AA genotype at +292 A>C was associated with a shorter PFS time.
| S-EPMC6063035 | biostudies-literature
Project description:Primary Objective:
Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.
Secondary Objectives:
Correlation of SNP profile with indicators of tumour response parameters, such as radiological response, duration of response, time to progression (TTP), overall survival (OS) time, incidence of non-dermatological adverse events.
| 2135070 | ecrin-mdr-crc
Project description:AIM:To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma. METHODS:Primary gastric carcinomas (n=80), their corresponding normal mucosal samples, and gastric mucosal biopsies from normal/gastritis control patients (n=54) were used. Hypermethylation at -253 nt and -251 nt in relation with the translational start site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter were analyzed by Bst UI-combined bisulfite assay (COBRA), denaturing high performance liquid chromatogram (DHPLC), and sequencing. RESULTS:(A) The specific methylation at -253 nt and -251 nt was observed in 2 of 60 primary gastric carcinomas, but neither in all of the corresponding mucosa nor in normal/gastritis samples, by Bst UI-COBRA and DHPLC. (B) The hMLH1 promoter was methylated homogeneously in the xenograft of the primary gastric carcinoma with the methylated and unmethylated hMLH1. (C) The pattern of SNP at -93 nt of the hMLH1 promoter in 54 Chinese patients with gastric carcinoma was the same as that in the control patients: 51 % was A/G heteroalleles, 34 % and 15 % were A/A and G/G homoalleles, respectively. CONCLUSION:Biallelic inactivation of hMLH1 by epigenetic silencing existed in human primary gastric carcinoma homogeneously. Hypermethylation of hMLH1 may play a role in the early stage of development of a few gastric carcinomas. The SNP at -93 nt is not related to the susceptibility of gastric carcinomas.
| S-EPMC4728242 | biostudies-literature
Project description:UNLABELLED:Ginger (Zingiber officinale Rosc) (Family: Zingiberaceae) is a herbaceous perennial, the rhizomes of which are used as a spice. Ginger is a plant which is well known for its medicinal applications. Recently EST-derived SNPs are a free by-product of the currently expanding EST (Expressed Sequence Tag) databases. The development of high-throughput methods for the detection of SNPs (Single Nucleotide Polymorphism) and small indels (insertion/deletion) has led to a revolution in their use as molecular markers. Available (38139) Ginger EST sequences were mined from dbEST of NCBI. CAP3 program was used to assemble EST sequences into contigs. Candidate SNPs and Indel polymorphisms were detected using the perl script AutoSNP version 1.0 which has used 31905 ESTs for detecting SNPs and Indel sites. We found 64026 SNP sites and 7034 indel polymorphisms with frequency of 0.84 SNPs / 100 bp. Among the three tissues from which the EST libraries had been generated, Rhizomes had high frequency of 1.08 SNPs/indels per 100 bp whereas the leaves had lowest frequency of 0.63 per 100 bp and root is showing relative frequency 0.82/100bp. Transitions and transversion ratio is 0.90. In overall detected SNP, transversion is high when compare to transition. These detected SNPs can be used as markers for genetic studies. AVAILABILITY:The results of the present study hosted in our webserver www.spices.res.in/spicesnip.
| S-EPMC2828891 | biostudies-literature
Project description:Camelina sativa, a largely relict crop, has recently returned to interest due to its potential as an industrial oilseed. Molecular markers are key tools that will allow C. sativa to benefit from modern breeding approaches. Two complementary methodologies, capture of 3' cDNA tags and genomic reduced-representation libraries, both of which exploited second generation sequencing platforms, were used to develop a low density (768) Illumina GoldenGate single nucleotide polymorphism (SNP) array. The array allowed 533 SNP loci to be genetically mapped in a recombinant inbred population of C. sativa. Alignment of the SNP loci to the C. sativa genome identified the underlying sequenced regions that would delimit potential candidate genes in any mapping project. In addition, the SNP array was used to assess genetic variation among a collection of 175 accessions of C. sativa, identifying two sub-populations, yet low overall gene diversity. The SNP loci will provide useful tools for future crop improvement of C. sativa.
| S-EPMC4300397 | biostudies-literature
Project description:BackgroundThe aim of this study was to investigate the correlation between MDM2 T309G single nucleotide polymorphism (SNP) and esophageal cancer susceptibility through pooling the open published data.MethodsBy systematic searching the databases of Medline, EMBASE, CBM and CNKI, the case-control or cohort studies related to MDM2 T309G single nucleotide polymorphism and esophageal cancer risk were screened. Genetic phenotype data of T309G single nucleotide was extracted from the original included studies. The correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility was demonstrated by the odds ratio (OR) and its corresponding 95% confidence interval (95% CI). Publication bias was investigated by Egger's line regression test and begg's funnel plot.ResultsAfter systematic searching of the relevant database, nine publications were finally included in the present study. The combined data demonstrated that the subjects with the G genotype had an increased risk of developing esophageal cancer in dominant (OR = 1.13, 95% CI: 1.00-1.27, P = 0.043), recessive (OR = 1.27, 95% CI: 1.12-1.45, P = 0.000) and homozygous (OR = 1.34, 95% CI:1.04-1.74, P = 0.024) genetic model through random or fixed data pooling method. Both begg's and Egger's line regression test indicated no significant publication bias.ConclusionBased on the present data, there was a significant correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility. Individuals with G genotype may have an increased risk of developing esophageal cancer.
| S-EPMC7049506 | biostudies-literature
Project description:BackgroundCurrent evidence of the association between a single nucleotide polymorphism (SNP) in ADAMTS14 (rs4747096) and osteoarthritis (OA) is controversial. This study aimed to determine whether the ADAMTS14 SNP is closely related to OA risk.MethodsAn electronic search of for the association between the rs4747096 polymorphisms and OA was performed using four online databases (updated on September 10, 2022). The association between susceptibility to OA and rs4747096 polymorphism was evaluated in four genetic models: the allele (mutation [A] vs. wild type [G]), additive (AA vs. GG and AG vs. GG), recessive (AA vs. AG + GG), and dominant (AA + AG vs. GG). This meta-analysis was performed in the R software, and effects were assessed using odds ratios (ORs) and 95% confidence intervals (CI).ResultsFour studies (707 cases in the case group and 859 cases in the control group) were included. The results of the meta-analysis showed that, except in the recessive genetic model, there was a significant correlation between OA risk and the rs4747096 polymorphism using the allele (OR [95% CI] = 1.48 [1.26-1.73], P < 0.001), additive (AG vs. GG, OR [95% CI] = 2.56 [1.79-3.65], P < 0.001; AA vs. GG, OR [95% CI] = 2.81 [1.98-3.98], P < 0.001), and dominant (OR [95% CI)] = 1.72 [1.34-2.2], P < 0.001) genetic models.ConclusionsThe ADAMTS14 rs4747096 polymorphism is associated with susceptibility to OA.
| S-EPMC10405498 | biostudies-literature
Project description:Major facilitators of water movement through plant cell membranes include aquaporin proteins. Wheat is among the largest and most important cereal crops worldwide; however, unlike other model plants such as rice, maize and Arabidopsis, little has been reported on wheat major intrinsic proteins (MIPs). This study presents a comprehensive computational identification of 349 new wheat expressed sequence tags (ESTs), encoding 13 wheat aquaporin genes. Identified aquaporins consist of 6 plasma membrane intrinsic proteins (PIP) and 1 TIP showing high sequence similarity with rice aquaporins. We also identified 4 NOD26-like intrinsic proteins (NIP) and 2 SIP members that showed more divergence. Further, expression analysis of the aquaporin genes using the available EST information in UniGene revealed their transcripts were differentially regulated in various stress- and tissue-specific libraries. Allele specific Polymerase chain reaction (PCR) primers based on single nucleotide polymorphism (SNP) were designed using PIP as the target gene and validated on a core set of Indian wheat genotypes. A 3D theoretical model of the wheat aquaporin protein was built by homology modeling and could prove to be useful in the further functional characterization of this protein. Collectively with expression and bioinformatics analysis, our results support the idea that the genes identified in this study signify an important genetic resource providing potential targets to modify the water use properties of wheat.
| S-EPMC3825567 | biostudies-literature
Project description:Primary brain tumors are a major cause of cancer mortality in the United States. Therapy for gliomas, the most common type of primary brain tumors, remains suboptimal. The development of improved therapeutics will require greater knowledge of the biology of gliomas at both the genomic and transcriptional levels. We have previously reported whole genome profiling of chromosome copy number alterations (CNA) in gliomas, and now present our findings on how those changes may affect transcription of genes that may be involved in tumor induction and progression. By calculating correlation values of mRNA expression versus DNA copy number average in a moving window around a given RNA probe set, biologically relevant information can be gained that is obscured by the analysis of a single data type. Correlation coefficients ranged from -0.6 to 0.7, highly significant when compared with previous studies. Most correlated genes are located on chromosomes 1, 7, 9, 10, 13, 14, 19, 20, and 22, chromosomes known to have genomic alterations in gliomas. Additionally, we were able to identify CNAs whose gene expression correlation suggests possible epigenetic regulation. This analysis revealed a number of interesting candidates such as CXCL12, PTER, and LRRN6C, among others. The results have been verified using real-time PCR and methylation sequencing assays. These data will further help differentiate genes involved in the induction and/or maintenance of the tumorigenic process from those that are mere passenger mutations, thereby enriching for a population of potentially new therapeutic molecular targets.
| S-EPMC2644341 | biostudies-literature