Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Yunyi, Liu, Zheng, Liu, Kuo, Qi, Han, Peng, Wenjuan, Cao, Han, Liu, Xiaohui, Li, Bingxiao, Wen, Fuyuan, Zhang, Fengxu, Zhang, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1784584814377041920
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
work_keys_str_mv AT xieyunyi candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT liuzheng candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT liukuo candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT qihan candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT pengwenjuan candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT caohan candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT liuxiaohui candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT libingxiao candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT wenfuyuan candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT zhangfengxu candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators
AT zhangling candidategenepolymorphismsinfluencethesusceptibilitytosaltsensitivityofbloodpressureinahanchinesepopulationriskfactorsasmediators