May 30, 2014Open Access
A Gene-Based Analysis of Variants in the Serum/Glucocorticoid Regulated Kinase (SGK) Genes with Blood Pressure Responses to Sodium Intake: The GenSalt Study
Key Result
The SGK1 gene variant rs2758151 was significantly associated with diastolic blood pressure response to high-sodium intake, with mean responses of 2.04, 1.79, and 0.85 mmHg for C/C, C/T, and T/T genotypes, respectively.
Study Design
Type
Observational (n=1,906)
Blinding
Single-blind
Multicenter
Yes
Structured PICO
Are variants in the SGK genes associated with blood pressure responses to dietary sodium intervention in a Han Chinese population?
P
Population
1,906 rural Han Chinese participants from 633 families (probands with untreated BP 130-160/85-100 mmHg and their relatives), mean age 38.7 years, 53.0% male. Excluded: stage-2 hypertension, current/recent antihypertensive use, secondary hypertension, history of clinical CVD, diabetes, CKD.
I
Intervention
7-day low-sodium dietary intervention (51.3 mmol sodium/day) followed by a 7-day high-sodium dietary intervention (307.8 mmol sodium/day)
C
Comparator
Baseline diet (3-day observation period) and low-sodium diet (for the high-sodium response comparison)
O
Outcome
Absolute changes in SBP, DBP, and MAP from baseline to low-sodium intervention and from low-sodium intervention to high-sodium interventionsurrogate
Genetic variants in the SGK1 gene are significantly associated with blood pressure salt-sensitivity in a Han Chinese population, highlighting a potential genomic mechanism for blood pressure regulation.
Main Result
p-value: p=0.0010
Limitations
- Limited genomic coverage of the SGK3 gene by the genotyping platform, potentially missing common variants.
- Inability to replicate findings in an independent East Asian sample due to the uniqueness of the salt-sensitivity phenotype.
- The identified variant rs2758151 is located downstream of the gene and is likely not the causal variant, but rather in linkage disequilibrium with it.
Abstract
BACKGROUND: Serum and glucocorticoid regulated kinase (SGK) plays a critical role in the regulation of renal sodium transport. We examined the association between SGK genes and salt sensitivity of blood pressure (BP) using single-marker and gene-based association analysis. METHODS: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Chinese participants. BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Additive associations between each SNP and salt-sensitivity phenotypes were assessed using a mixed linear regression model to account for family dependencies. Gene-based analyses were conducted using the truncated p-value method. The Bonferroni-method was used to adjust for multiple testing in all analyses. RESULTS: In single-marker association analyses, SGK1 marker rs2758151 was significantly associated with diastolic BP (DBP) response to high-sodium intervention (P = 0.0010). DBP responses (95% confidence interval) to high-sodium intervention for genotypes C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30 to 1.41) mmHg, respectively. Similar trends were observed for SBP and MAP responses although not significant (P = 0.15 and 0.0026, respectively). In addition, gene-based analyses demonstrated significant associations between SGK1 and SBP, DBP and MAP responses to high sodium intervention (P = 0.0002, 0.0076, and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt-sensitivity phenotypes in single-maker or gene-based analyses. CONCLUSIONS: The current study identified association of the SGK1 gene and BP salt-sensitivity in the Han Chinese population. Further studies are warranted to identify causal SGK1 gene variants.