title: Common genetic variants in the endothelial system predict blood pressure response to sodium intake: the GenSalt study.
abstract: BACKGROUND We examined the association between 14 endothelial system genes and salt-sensitivity of blood pressure (BP). METHODS After a 3-day baseline examination, during which time the usual diet was consumed, 1,906 Chinese participants received a 7-day low-sodium diet (51.3 mmol of sodium/day) followed by a 7-day high-sodium diet (307.8 mmol of sodium/day). BP measurements were obtained at baseline and at the end of each intervention using a random-zero sphygmomanometer. RESULTS The DDAH1 rs11161637 variant was associated with reduced BP salt sensitivity, conferring attenuated systolic BP (SBP) and mean arterial pressure (MAP) decreases from baseline to the low-sodium intervention (both P = 2×10(-4)). Examination of genotype-sex interactions revealed that this relation was driven by the strong associations observed in men (P for interactions = 1.10×10(-4) and 0.008, respectively). When switching from the low- to high-sodium intervention, increases in diastolic BP (DBP) and MAP were attenuated by the COL18A1 rs2838944 minor A allele (P = 1.41×10(-4) and 1.55×10(-4), respectively). Conversely, the VWF rs2239153 C variant was associated with increased salt sensitivity, conferring larger DBP and MAP reductions during low-sodium intervention (P = 1.22×10(-4) and 4.44×10(-5), respectively). Ten variants from 3 independent SELE loci displayed significant genotype-sex interactions on DBP and MAP responses to low-sodium (P for interaction = 1.56×10(-3) to 1.00×10(-4)). Among men, minor alleles of 4 correlated markers attenuated BP responses to low-sodium intake, whereas minor alleles of another 4 correlated markers increased BP responses. No associations were observed in women for these variants. Further, qualitative interactions were shown for 2 correlated SELE markers. CONCLUSIONS These data support a role for the endothelial system genes in salt sensitivity.
authors: Centro de Excelencia en Salud Cardiovascular para el Cono Sur, Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina.
authors: Maria Daniela
authors: MD
authors: Defagó
authors: Dongfeng
authors: D
authors: Gu
authors: James E
authors: JE
authors: Hixson
authors: Lawrence C
authors: LC
authors: Shimmin
authors: Treva K
authors: TK
authors: Rice
authors: Charles C
authors: CC
authors: Gu
authors: Cashell E
authors: CE
authors: Jaquish
authors: De-Pei
authors: DP
authors: Liu
authors: Jiang
authors: J
authors: He
authors: Tanika N
authors: TN
authors: Kelly
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D004039:Diet, Sodium-Restricted; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D024021:Fibril-Associated Collagens / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D012982:Sodium, Dietary / Q000494:pharmacology*; D055815:Young Adult; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: C534489:COL19A1 protein, human; D019040:E-Selectin; D024021:Fibril-Associated Collagens; C546936:SELE protein, human; D012982:Sodium, Dietary; D014841:von Willebrand Factor; D000581:Amidohydrolases; C059999:dimethylargininase