title: Analysis of sex hormone genes reveals gender differences in the genetic etiology of blood pressure salt sensitivity: the GenSalt study.
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.
authors: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. tkelly@tulane.edu
authors: Tanika N
authors: TN
authors: Kelly
authors: Casey M
authors: CM
authors: Rebholz
authors: Dongfeng
authors: D
authors: Gu
authors: James E
authors: JE
authors: Hixson
authors: Treva K
authors: TK
authors: Rice
authors: Jie
authors: J
authors: Cao
authors: Jichun
authors: J
authors: Chen
authors: Jianxin
authors: J
authors: Li
authors: Fanghong
authors: F
authors: Lu
authors: Jixiang
authors: J
authors: Ma
authors: Jianjun
authors: J
authors: Mu
authors: Paul K
authors: PK
authors: Whelton
authors: Jiang
authors: J
authors: He
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D002681:China; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005796:Genes; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics; D012737:Sex Factors; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D017673:Sodium Chloride, Dietary
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