Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression

Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium thro...

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Autores principales:	Jia-Wen Hu, Tao Shi, Jian-Jun Mu
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	klotho single-nucleotide polymorphisms salt sensitivity potassium sensitivity blood pressure Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/e8f4e35083fd4a499835c3b71222a4fb
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spelling	oai:doaj.org-article:e8f4e35083fd4a499835c3b71222a4fb2021-12-02T12:40:22ZAssociation of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression1420-40961423-014310.1159/000519839https://doaj.org/article/e8f4e35083fd4a499835c3b71222a4fb2021-12-01T00:00:00Zhttps://www.karger.com/Article/FullText/519839https://doaj.org/toc/1420-4096https://doaj.org/toc/1423-0143Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. Methods: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. Results: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (β = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (β = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (β = 20.47, p = 0.032). Conclusions: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension.Jia-Wen HuTao ShiJian-Jun MuKarger Publishersarticleklothosingle-nucleotide polymorphismssalt sensitivitypotassium sensitivityblood pressureDermatologyRL1-803Diseases of the circulatory (Cardiovascular) systemRC666-701Diseases of the genitourinary system. UrologyRC870-923ENKidney & Blood Pressure Research, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	klotho single-nucleotide polymorphisms salt sensitivity potassium sensitivity blood pressure Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923
spellingShingle	klotho single-nucleotide polymorphisms salt sensitivity potassium sensitivity blood pressure Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923 Jia-Wen Hu Tao Shi Jian-Jun Mu Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
description	Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. Methods: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. Results: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (β = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (β = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (β = 20.47, p = 0.032). Conclusions: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension.
format	article
author	Jia-Wen Hu Tao Shi Jian-Jun Mu
author_facet	Jia-Wen Hu Tao Shi Jian-Jun Mu
author_sort	Jia-Wen Hu
title	Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
title_short	Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
title_full	Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
title_fullStr	Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
title_full_unstemmed	Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression
title_sort	association of genetic variants of klotho with bp responses to dietary sodium or potassium intervention and long-term bp progression
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/e8f4e35083fd4a499835c3b71222a4fb
work_keys_str_mv	AT jiawenhu associationofgeneticvariantsofklothowithbpresponsestodietarysodiumorpotassiuminterventionandlongtermbpprogression AT taoshi associationofgeneticvariantsofklothowithbpresponsestodietarysodiumorpotassiuminterventionandlongtermbpprogression AT jianjunmu associationofgeneticvariantsofklothowithbpresponsestodietarysodiumorpotassiuminterventionandlongtermbpprogression
_version_	1718393773362249728

Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression

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