A gene-based analysis of variants in the serum/glucocorticoid regulated kinase (SGK) genes with blood pressure responses to sodium intake: the GenSalt Study.
A gene-based analysis of variants in the serum/glucocorticoid regulated kinase (SGK) genes with blood pressure responses to sodium intake: the GenSalt Study.
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DOI：
10.1371/journal.pone.0098432
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kelly TN
中科院分区：
文献类型：
--
作者：
Li C;Yang X;He J;Hixson JE;Gu D;Rao DC;Shimmin LC;Huang J;Gu CC;Chen J;Li J;Kelly TN
血清和糖皮质激素调节激酶（SGK）在肾脏钠转运的调节中起着关键作用。我们使用单标记和基于基因的关联分析研究了SGK基因与血压盐敏感性之间的关联。在1,906名中国受试者中进行了7天的低钠（51.3 mmol钠/天），随后进行了7天的高钠干预（307.8 mmol钠/天）。在基线和每次干预时使用随机调零血压计测量血压。使用混合线性回归模型评估每个SNP和盐敏感性表型之间的加性关联，以解释家族依赖性。使用截断p值方法进行基于基因的分析。在所有分析中，使用Bonferroni方法调整多重检验。在单标志物相关性分析中，SGK 1标志物rs 2758151与高钠干预的舒张压（DBP）反应显著相关（P = 0.0010）。 C/C、C/T和T/T基因型对高钠干预的DBP反应（95%置信区间）分别为2.04（1.57 - 2.52）、1.79（1.42 - 2.16）和0.85（0.30 - 1.41）mmHg。SBP和MAP反应观察到类似趋势，但不显著（分别为P=0.15和0.0026）。 此外，基于基因的分析表明SGK 1与高钠干预的SBP、DBP和MAP反应之间存在显著相关性（分别为P=0.0002、0.0076和0.00001）。 在单标记或基于基因的分析中，SGK 2和SGK 3均与盐敏感性表型无关。目前的研究确定了SGK 1基因和BP盐敏感性在中国汉族人群中的关联。进一步的研究是必要的，以确定因果SGK 1基因变异。
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. 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. 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. 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.
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影响因子：
2.7
作者：
通讯作者：
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DOI：
10.1152/ajprenal.00535.2011
发表时间：
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影响因子：
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