Dataset Information

Associations between potentially functional CORIN SNPs and serum corin levels in the Chinese Han population.

ABSTRACT: BACKGROUND:Corin is an important convertase involved in the natriuretic peptide system and may indirectly regulate blood pressure. Genetic factors relate to corin remain unclear. The purpose of the current study was to comprehensively examine the associations among CORIN SNPs, methylations, serum corin levels and hypertension. RESULTS:We genotyped 9 tag-SNPs in the CORIN gene and measured serum corin levels in 731 new-onset hypertensive cases and 731 age- and sex-matched controls. DNA methylations were tested in 43 individuals. Mendelian randomization was used to investigate the causal associations. Under additive models, we observed associations of rs2289433 (p.Cys13Tyr), rs6823184, rs10517195, rs2271037 and rs12509275 with serum corin levels after adjustment for covariates (P?=?0.0399, 0.0238, 0.0016, 0.0148 and 0.0038, respectively). The tag-SNP rs6823184 and SNPs that are in strong linkage disequilibrium with it, i.e., rs10049713, rs6823698 and rs1866689, were associated with CORIN gene expression (P?=?2.38?×?10-?24, 5.94?×?10-?27, 6.31?×?10-?27 and 6.30?×?10-?27, respectively). Neither SNPs nor corin levels was found to be associated with hypertension. SNP rs6823184, which is located in a DNase hypersensitivity cluster, a CpG island and transcription factor binding sites, was significantly associated with cg02955940 methylation levels (P?=?1.54?×?10-?7). A putative causal association between cg02955940 methylation and corin levels was detected (P?=?0.0011). CONCLUSION:This study identified potentially functional CORIN SNPs that were associated with serum corin level in the Chinese Han population. The effect of CORIN SNPs on corin level may be mediated by DNA methylation.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6923953 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Associations between potentially functional CORIN SNPs and serum corin levels in the Chinese Han population.

Zhang Huan H Mo Xingbo X Qian Qiyu Q Zhou Zhengyuan Z Zhu Zhengbao Z HuangFu Xinfeng X Xu Tan T Wang Aili A Guo Zhirong Z Lei Shufeng S Zhang Yonghong Y

BMC genetics 20191219 1

<h4>Background</h4>Corin is an important convertase involved in the natriuretic peptide system and may indirectly regulate blood pressure. Genetic factors relate to corin remain unclear. The purpose of the current study was to comprehensively examine the associations among CORIN SNPs, methylations, serum corin levels and hypertension.<h4>Results</h4>We genotyped 9 tag-SNPs in the CORIN gene and measured serum corin levels in 731 new-onset hypertensive cases and 731 age- and sex-matched controls. ...[more]

PMID: 31856714

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Project description:Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes.

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Dataset Information

Associations between potentially functional CORIN SNPs and serum corin levels in the Chinese Han population.

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Associations between potentially functional CORIN SNPs and serum corin levels in the Chinese Han population.

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