Dataset Information

MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population.

ABSTRACT: Recently, MDM4 gene has been reported to be a susceptibility gene for glioma in Europeans, but the molecular mechanism of glioma pathogenesis remains unknown. The aim of this study was to investigate whether common variants of MDM4 contribute to the risk of glioma in Han Chinese individuals. A total of 24 single-nucleotide polymorphisms (SNPs) of the MDM4 gene were assessed in a dataset of 562 glioma patients (non-glioblastoma) and 1,192 cancer-free controls. The SNP rs4252707 was found to be strongly associated with the risk of non-GBM (P?=?0.000101, adjusted odds ratio (OR)?=?1.34, 95% confidence interval (CI)?=?1.16-1.55). Further analyses indicated that there was a significant association between A allele of rs4252707 associated with the increased non-GBM risk. Haplotype analysis also confirmed a result similar to that of the single-SNP analysis. Using stratification analyses, we found the association of rs4252707 with an increased non-GBM risk in adults (?18 years, P?=?0.0016) and individuals without IR exposure history (P?=?0.0013). Our results provide strong evidence that the MDM4 gene is tightly linked to genetic susceptibility for non-GBM risk in Han Chinese population, indicating a important role for MDM4 gene in the etiology of glioma.

SUBMITTER: Sun P

PROVIDER: S-EPMC6056491 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population.

Sun Peng P Yan Feng F Fang Wei W Zhao Junjie J Chen Hu H Ma Xudong X Song Jinning J

Scientific reports 20180723 1

Recently, MDM4 gene has been reported to be a susceptibility gene for glioma in Europeans, but the molecular mechanism of glioma pathogenesis remains unknown. The aim of this study was to investigate whether common variants of MDM4 contribute to the risk of glioma in Han Chinese individuals. A total of 24 single-nucleotide polymorphisms (SNPs) of the MDM4 gene were assessed in a dataset of 562 glioma patients (non-glioblastoma) and 1,192 cancer-free controls. The SNP rs4252707 was found to be st ...[more]

PMID: 30038284

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Project description:BackgroundlncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear.MethodsIn the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs.ResultsWe found that rs7318578 (OR = 2.25, p = 3.18 × 10- 5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age < 40 years, rs17735387 (OR = 1.53, p = 9.05 × 10- 3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with I-II glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ≥ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002).ConclusionOur study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis. In subsequent studies, we will continue to collect samples and follow up to further validate our findings and further explore the function of these MIR17HG SNPs in glioma in a larger sample size.

Project description:Objective:Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods:We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results:Significant associations were found in genotype and allele frequencies for SNPs rs10815017 (p = 0.002, 0.030, respectively) and rs2026828 (p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 (p = 0.020) and rs7024664 (p = 0.021) and allele frequency at rs3780412 (p = 0.026) and rs10974573 (p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 (p = 0.015), rs2026828 (p = 0.011), and rs3780411 (p = 0.040) in males, and rs7021569 in females (p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 (p = 0.003), and rs7021569 (p = 0.045) in males, and rs10974619 in females (p = 0.044). However, those associations disappeared after Bonferroni's correction (p's > 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls (? 2 = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ (p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion:The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms.

Dataset Information

MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population.

Publications

MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population.

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