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Variants in the SMARCA4 gene was associated with coronary heart disease susceptibility in Chinese han population.

ABSTRACT: Coronary heart disease (CHD) is the leading cause of death worldwide. Many single-nucleotide polymorphisms (SNPs) are found to be related to the risk of CHD in previous studies. This study investigated whether polymorphism of SMARCA4 gene is associated with CHD.Genotypes at five CHD-relevant SNPs were determined in 456 cases of incident CHD and 685 unaffected controls in Chinese Han population using ?2 test, genetic model analysis and haplotype analysis. We also analysis the differences in continuous variables among the subjects with three genotypes of related genes were assessed using the ANOVA.We identified two susceptibility SNPs in the SMARCA4 gene that were potentially associated with a decreased risk of CHD. We identified rs11879293 (OR, 0.74; 95% CI, 0.59-0.96; P = 0.012) and rs12232780 (OR, 0.70; 95% CI, 0.54-0.90; P = 0.005) were associated with a decreased risk of CHD risk under the log-additive model adjusted by gender and age. Meanwhile, we also found that significant differences in glucose concentrations with rs11879293 and rs1122608 different genotype. Serum LDL-C and HDL-C were seen among the 3 genotypes of rs12232780 exist differences.This study provides an evidence for polymorphism of SMARCA4 gene associated with CHD development in Chinese Han population.

SUBMITTER: Guo X

PROVIDER: S-EPMC5352326 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Variants in the SMARCA4 gene was associated with coronary heart disease susceptibility in Chinese han population.

Guo Xuan X Wang Xiaohong X Wang Yuan Y Zhang Chunyan C Quan Xiaohui X Zhang Yan Y Jia Shan S Ma Weidong W Fan Yajie Y Wang Congxia C

Oncotarget 20170101 5

<h4>Background</h4>Coronary heart disease (CHD) is the leading cause of death worldwide. Many single-nucleotide polymorphisms (SNPs) are found to be related to the risk of CHD in previous studies. This study investigated whether polymorphism of SMARCA4 gene is associated with CHD.<h4>Materials and methods</h4>Genotypes at five CHD-relevant SNPs were determined in 456 cases of incident CHD and 685 unaffected controls in Chinese Han population using χ2 test, genetic model analysis and haplotype an ...[more]

PMID: 28055962

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Project description:INTRODUCTION: Deregulated or excessive host immune responses contribute to the pathogenesis of sepsis. Toll-like receptor (TLR) signaling pathways and their negative regulators play a pivotal role in the modulation of host immune responses and the development of sepsis. The objective of this study was to investigate the association of variants in the TLR signaling pathway genes and their negative regulator genes with susceptibility to sepsis in the Chinese Han population. METHODS: Patients with severe sepsis (n = 378) and healthy control subjects (n = 390) were enrolled. Five genes, namely TLR2, TLR4, TLR9, MyD88 and TOLLIP, were investigated for their association with sepsis susceptibility by a tag single nucleotide polymorphism (SNP) strategy. Twelve tag SNPs were selected based on the data of Chinese Han in Beijing from the HapMap project and genotyped by direct sequencing. The mRNA expression levels of TOLLIP were determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of tumor necrosis factor alpha (TNF-?) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our results showed that the minor C-allele of rs5743867 in TOLLIP was significantly associated with the decreased risk of sepsis (Padj = 0.00062, odds ratio (OR)adj = 0.71, 95% confidence interval (CI) 0.59 to 0.86) after adjustment for covariates in multiple logistic regression analysis. A 3-SNP haplotype block harboring the associated SNP rs5743867 also displayed strong association with omnibus test P value of 0.00049. Haplotype GTC showed a protective role against sepsis (Padj = 0.0012), while haplotype GCT showed an increased risk for sepsis (Padj = 0.00092). After exposure to lipopolysaccharide (LPS), TOLLIP mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from homozygotes for the rs5743867C allele were significantly higher than in heterozygotes and homozygotes for the rs5743867T allele (P = 0.013 and P = 0.01, respectively). Moreover, the concentrations of TNF-? and IL-6 in culture supernatants were significantly lower in the subjects of rs5743867CC genotype than in CT and TT genotype subjects (P = 0.016 and P = 0.003 for TNF-?; P = 0.01 and P = 0.002 for IL-6, respectively). CONCLUSIONS: Our findings indicated that the variants in TOLLIP were significantly associated with sepsis susceptibility in the Chinese Han population.

Dataset Information

Variants in the SMARCA4 gene was associated with coronary heart disease susceptibility in Chinese han population.

Publications

Variants in the SMARCA4 gene was associated with coronary heart disease susceptibility in Chinese han population.

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