Association Between Blood Pressure Responses to the Cold Pressor Test and Dietary Sodium Intervention in a Chinese Population

Chen, Jing; Gu, Dongfeng; Jaquish, Cashell E.; Chen, Chung Shiuan; Rao, D. C.; Liu, Depei; Hixson, James E.; Hamm, L. Lee; Gu, C. Charles; He, Jiang

doi:10.1001/archinte.168.16.1740

Cited by 29 publications

(24 citation statements)

References 33 publications

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“…While we were mapping for the BP QTL reported in this study, a GWAS reported the association of a region on human chromosome 2q37 to systolic BP responses to cold pressor test, which was also previously demonstrated by the same group to be associated with salt sensitivity (13,44). This region on human chromosome 2q37 is homologous to the rat BP QTL reported in the current study and near the human TRPM8 and SPP2 loci.…”

Section: Discussionsupporting

confidence: 81%

High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass

Nie

Kumarasamy

Waghulde

et al. 2016

Physiological Genomics

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Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass.

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Section: Discussionsupporting

confidence: 81%

High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass

Nie

Kumarasamy

Waghulde

et al. 2016

Physiological Genomics

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“…There may also be a genetic predisposition to SS 7, 9 . Finally the GenSalt Study recently reported an association of SS with the BP response to the cold pressor test (CPT), suggesting a role for sympathetic nervous function in the development of SS 10 .…”

Section: Introductionmentioning

confidence: 99%

Determinants of Blood Pressure Response to Low‐Salt Intake in a Healthy Adult Population

Montasser

Douglas

Roy-Gagnon

et al. 2011

J of Clinical Hypertension

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Although the beneficial effects of lowering salt intake in hypertensives are widely appreciated, the impact of promoting dietary salt restriction for BP reduction at the population level remains controversial. We used 24-hr ambulatory blood pressure monitoring to characterize the determinants of systolic blood pressure (SBP) response to low salt intake in a large, relatively healthy Amish population. Subjects received a high and low sodium diet for 6 days each, separated by a 6–14 day washout period. Variance component analysis was used to assess the association of several variables with SBP response to low salt diet. Mean SBP was 0.7 ± 5.8 and 1.3 ± 6.1 mmHg lower on the low salt compared to the high salt diet during daytime (p=0.008) and nighttime (p<0.0001) respectively. SBP response to low salt diet was significantly associated with increasing age and pre-intervention SBP, in both daytime and nighttime, while the association with female gender and SBP response to cold pressor test (CPT) was significant only during nighttime. Our results suggest that salt reduction may have greater BP-lowering effects on females, older individuals, individuals with higher SBP, and individuals with higher SBP response to CPT.

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“…6 BP response to CPT has also been associated with salt-sensitivity of BP. 7 Twin studies and pedigree studies have suggested that BP response to CPT has strong genetic determinants. 8 …”

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confidence: 99%

Genome-Wide Association Study Identifies 8 Novel Loci Associated With Blood Pressure Responses to Interventions in Han Chinese

He¹,

Kelly²,

Zhao³

et al. 2013

Circ Cardiovasc Genet

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Background Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test (CPT) vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and CPT. Methods and Results We conducted a genome-wide association study of BP responses in 1,881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/day), a 7-day high-sodium (307.8 mmol/day), and a 7-day high-sodium plus potassium-supplementation (60 mmol/day). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified eight novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29×10−9), CDCA7 (P=3.57×10−8), PIBF1 (P=1.78×10−9), ARL4C (P=1.86×10−8), IRAK1BP1 (P=1.44×10−10), SALL1 (P=7.01×10−13), TRPM8 (P=2.68×10−8), and FBXL13 (P=3.74×10−9). There was a strong dose-response relationship between the number of risk alleles of these independent SNPs and the risk of developing hypertension over 7.5-year follow-up in the study participants. Compared to those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend). Conclusions Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and CPT. The effect size of these novel loci on BP phenotypes are much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.

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Association Between Blood Pressure Responses to the Cold Pressor Test and Dietary Sodium Intervention in a Chinese Population

Cited by 29 publications

References 33 publications

High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass

High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass

Determinants of Blood Pressure Response to Low‐Salt Intake in a Healthy Adult Population

Genome-Wide Association Study Identifies 8 Novel Loci Associated With Blood Pressure Responses to Interventions in Han Chinese

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