Dataset Information

Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

ABSTRACT: BACKGROUND:Human heparanase plays an important role in cancer development and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be correlated with gastric cancer. The present study examined the associations between individual SNPs or haplotypes in HPSE and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China. METHODOLOGY/PRINCIPAL FINDINGS:Genomic DNA was extracted from formalin-fixed, paraffin-embedded normal gastric tissue samples from 404 patients and from blood from 404 healthy controls. Six SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A chi-square (?2) test and unconditional logistic regression were used to analyze the risk of gastric cancer; a Log-rank test and Cox proportional hazards model were used to produce survival analysis and a Kaplan-Meier method was used to map survival curves. The mean genotyping success rates were more than 99% in both groups. Haplotype CA in the block composed of rs11099592 and rs4693608 had a greater distribution in the group of Borrmann types 3 and 4 (P?=?0.037), the group of a greater number of lymph node metastases (N3 vs N0 group, P?=?0.046), and moreover was correlated to poor survival (CG vs CA: HR?=?0.645, 95%CI: 0.421-0.989, P?=?0.044). In addition, genotypes rs4693608 AA and rs4364254 TT were associated with poor survival (P?=?0.030, HR?=?1.527, 95%CI: 1.042-2.238 for rs4693608 AA; P?=?0.013, HR?=?1.546, 95%CI: 1.096-2.181 for rs4364254 TT). There were no correlations between individual SNPs or haplotypes and gastric cancer risk. CONCLUSIONS/SIGNIFICANCE:A functional haplotype in HPSE was found, which included the important SNP rs4693608. SNPs in HPSE play an important role in gastric cancer progression and survival, and perhaps may be a molecular marker for prognosis and treatment values.

SUBMITTER: Li AL

PROVIDER: S-EPMC3262795 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

Li Ai-Lin AL Song Yong-Xi YX Wang Zhen-Ning ZN Gao Peng P Miao Yuan Y Zhu Jin-Liang JL Yue Zhen-Yu ZY Xu Hui-Mian HM

PloS one 20120120 1

<h4>Background</h4>Human heparanase plays an important role in cancer development and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be correlated with gastric cancer. The present study examined the associations between individual SNPs or haplotypes in HPSE and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China.<h4>Methodology/principal findings</h4>Genomic DNA was extra ...[more]

PMID: 22276173

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Project description:Objectives: Interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) is a very important immunomodulatory gene for autoimmune diseases located on the X chromosome. However, there was little study about the correlation of IRAK1 functional single nucleotide polymorphisms with mRNA expression in neuromyelitis optica spectrum disorder (NMOSD) patients. In this study, we aimed to investigate the plausible association of IRAK1 polymorphism, IRAK1 mRNA expression, and NMOSD risk in the northern Chinese Han population. Methods: Four loci of IRAK1 gene (rs1059702, rs7061789, rs1059703, and rs3027898) were genotyped using multiplex SNaPshot technique in 102 NMOSD patients and 213 healthy subjects. Allele, genotype, and haplotype frequencies were compared. Stratified analyses were conducted by age, sex, AQP4 status, and age of onset. IRAK1 mRNA levels in the peripheral blood mononuclear cells of 30 NMOSD patients (of active phase) and 15 healthy control subjects were detected using qPCR. The correlations between the SNP polymorphisms and mRNA expression levels of genes were tested using non-parametric tests. Results: The minor allele frequencies (MAF) of these four locis were significantly lower in NMOSD cases than that of the controls. The frequencies of rs1059703G/G genotype, rs1059702A/A genotype, rs3027898 C/C genotype, and rs7061789G/G genotype were higher in the case group than that of the control group. Haplotype analysis revealed that the major haplotype "G-A-C-G" (alleles in the order of SNPs rs1059703, rs1059702, rs3027898, and rs7061789), containing the risk alleles, conferred an adverse effect on NMOSD. The level of IRAK1mRNA was markedly higher in NMOSD when compared to the healthy control groups. The IRAK1mRNA levels of female patients with the major haplotype were significantly higher compared to those with other haplotypes and to the male patients with the same genotype. Conclusion: IRAK1 polymorphisms were highly correlated with NMOSD susceptibility. Its haplotype G-A-C-G (rs1059703-rs1059702-rs3027898-rs7061789) confers increasing the risk of NMOSD in female patients. The IRAK1 risk haplotype G-A-C-G upregulated IRAK1 mRNA expression in female NMOSD patients. Our study provides a novel insight into the molecular mechanism of the pathogenesis of NMOSD and reveals that IRAK1 is the potential mechanism-specific druggable target in NMOSD disease.

Dataset Information

Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

Publications

Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

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