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

Authors
  • Zhang, Huan1, 2
  • Mo, Xingbo1, 2, 1
  • Qian, Qiyu1, 2
  • Zhou, Zhengyuan3
  • Zhu, Zhengbao1, 2
  • HuangFu, Xinfeng1, 2
  • Xu, Tan1, 2
  • Wang, Aili1, 2
  • Guo, Zhirong1, 2
  • Lei, Shufeng1, 2, 1
  • Zhang, Yonghong1, 2
  • 1 Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China , Suzhou (China)
  • 2 Medical College of Soochow University, Suzhou, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu, 215123, People’s Republic of China , Suzhou (China)
  • 3 Changshu Center of Disease Control and Prevention, Suzhou, Jiangsu, People’s Republic of China , Suzhou (China)
Type
Published Article
Journal
BMC Genetics
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 19, 2019
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12863-019-0802-4
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundCorin 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.ResultsWe 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).ConclusionThis 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.

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