Analysis of sex hormone genes reveals gender differences in the genetic etiology of blood pressure salt sensitivity: The gensalt study

Tanika N. Kelly, Casey M. Rebholz, Dongfeng Gu, James E. Hixson, Treva K. Rice, Jie Cao, Jichun Chen, Jianxin Li, Fanghong Lu, Jixiang Ma, Jianjun Mu, Paul K. Whelton, Jiang He

Research output: Contribution to journalArticle

Abstract

Background We examined the association between 799 single-nucleotide polymorphisms in 39 sex hormone genes and blood pressure (BP) responses to a dietary-sodium intervention. Methods A 7-day low-sodium feeding study (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. Results Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453, rs9371562, rs9397459, and rs9383951. For example, mean diastolic blood pressure (DBP) responses to low-sodium intervention (95% confidence interval) were-2.67 (-3.13,-2.22) mm Hg among those with the rs9397453 C/C genotype,-1.23 (-1.98,-0.48) mm Hg among those with the C/T genotype, and 0.08 (-2.31, 2.47) mm Hg among those with the T/T genotype (P = 1×10-4; false discovery rate (FDR)-q = 0.04). Mean DBP responses to high sodium according to the rs9397453 genotypes were 1.46 (1.03, 1.89) mm Hg among those with C/C, 0.19 (-0.54, 0.91) mm Hg among those with C/T, and-1.10 (-2.82, 0.61) mm Hg among those with T/T (P = 2×10-4; FDR-q = 0.04). Similar trends were noted for the association between these ESR1 variants and SBP responses to the dietary intervention. There were no significant associations between sex hormone gene variants and salt sensitivity in women, with genotype-gender interactions noted for the ESR1 markers that achieved significance in men. Conclusions We identified strong, consistent associations between ESR1 gene variants and salt sensitivity in men. Our Results support a gender-specific role for ESR1 in the etiology of this complex trait.

Original languageEnglish (US)
Pages (from-to)191-200
Number of pages10
JournalAmerican Journal of Hypertension
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • blood pressure
  • dietary sodium
  • gender
  • genetics
  • hypertension
  • polymorphism
  • salt sensitivity

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Kelly, T. N., Rebholz, C. M., Gu, D., Hixson, J. E., Rice, T. K., Cao, J., Chen, J., Li, J., Lu, F., Ma, J., Mu, J., Whelton, P. K., & He, J. (2013). Analysis of sex hormone genes reveals gender differences in the genetic etiology of blood pressure salt sensitivity: The gensalt study. American Journal of Hypertension, 26(2), 191-200. https://doi.org/10.1093/ajh/hps018