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Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators
Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521039/ https://www.ncbi.nlm.nih.gov/pubmed/34671380 http://dx.doi.org/10.3389/fgene.2021.675230 |
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author | Xie, Yunyi Liu, Zheng Liu, Kuo Qi, Han Peng, Wenjuan Cao, Han Liu, Xiaohui Li, Bingxiao Wen, Fuyuan Zhang, Fengxu Zhang, Ling |
author_facet | Xie, Yunyi Liu, Zheng Liu, Kuo Qi, Han Peng, Wenjuan Cao, Han Liu, Xiaohui Li, Bingxiao Wen, Fuyuan Zhang, Fengxu Zhang, Ling |
author_sort | Xie, Yunyi |
collection | PubMed |
description | Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan’s acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes (P < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction (P < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects (P < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects (P < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators. |
format | Online Article Text |
id | pubmed-8521039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85210392021-10-19 Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators Xie, Yunyi Liu, Zheng Liu, Kuo Qi, Han Peng, Wenjuan Cao, Han Liu, Xiaohui Li, Bingxiao Wen, Fuyuan Zhang, Fengxu Zhang, Ling Front Genet Genetics Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan’s acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes (P < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction (P < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects (P < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects (P < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators. Frontiers Media S.A. 2021-10-04 /pmc/articles/PMC8521039/ /pubmed/34671380 http://dx.doi.org/10.3389/fgene.2021.675230 Text en Copyright © 2021 Xie, Liu, Liu, Qi, Peng, Cao, Liu, Li, Wen, Zhang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Xie, Yunyi Liu, Zheng Liu, Kuo Qi, Han Peng, Wenjuan Cao, Han Liu, Xiaohui Li, Bingxiao Wen, Fuyuan Zhang, Fengxu Zhang, Ling Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title | Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title_full | Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title_fullStr | Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title_full_unstemmed | Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title_short | Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators |
title_sort | candidate gene polymorphisms influence the susceptibility to salt sensitivity of blood pressure in a han chinese population: risk factors as mediators |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521039/ https://www.ncbi.nlm.nih.gov/pubmed/34671380 http://dx.doi.org/10.3389/fgene.2021.675230 |
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