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Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

ABSTRACT: We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P?1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium.

SUBMITTER: Li C

PROVIDER: S-EPMC5373034 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

Li Changwei C He Jiang J Chen Jing J Zhao Jinying J Gu Dongfeng D Hixson James E JE Rao Dabeeru C DC Jaquish Cashell E CE Gu Charles C CC Chen Jichun J Huang Jianfeng J Chen Shufeng S Kelly Tanika N TN

Hypertension (Dallas, Tex. : 1979) 20160606 2

We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleo ...[more]

PMID: 27271309

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Project description:BackgroundWhile salt sensitivity of blood pressure (SSBP) is a risk factor for hypertension, end-organ damage and death, most studies are conducted in western countries and in White people. We previously found that the prevalence of SSBP in Blacks living in Sub-Saharan Africa is as high as 75-80% like what has been reported in the west. Erythrocyte glycocalyx sensitivity to sodium (eGCSS), a marker of sodium-induced damage to the erythrocyte and vascular endothelial glycocalyx is thought to be related to blood pressure perturbations associated with salt intake. We hypothesized that SSBP correlates with eGCSS differently in men and women in Black people.MethodsWe conducted a cross sectional study using data from our recent clinical trial from Livingstone University Teaching Hospital among 117 normotensive young adults. We used a "salt blood test" to determine eGCSS and an immediate pressor response to oral salt (IPROS) for the diagnosis of SSBP.ResultsThe proportion of males were equal to females and the median age (interquartile range) of the participants was 29 (22-45) years. The eGCSS scores were higher in salt-resistant females compared to salt-sensitive females and males. eGCSS correlated negatively with SSBP (AOR 0.98, 95% CI 0.97-0.99, p = 0.008), however, this relationship was driven by female sex and abrogated by male sex. Although blood pressure elevations exhibited a sustained bimodal pattern in both sexes, in males, systolic and diastolic blood pressure never returned to baseline during the time course as it did in females.ConclusionIn this study, eGCSS correlated negatively with SSBP in black women but not in black men and the pressor response to dietary salt was significantly higher in men compared to women. These results suggest that women tend to have a higher disruption of the vascular endothelial glycocalyx by an acute salt load, implying that acute changes in blood pressure may not be driven directly by the endothelial glycocalyx. Our findings suggest a novel mechanism linking eGCSS and SSBP with potential implications for sex differences in salt-induced cardiovascular disease.Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT04844255].

Dataset Information

Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

Publications

Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

Similar Datasets

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