Association of Genetic Variants of <b><i>Klotho</i></b> with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression

Abstract

&lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; Klotho (&lt;i&gt;KL&lt;/i&gt;) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with &lt;i&gt;KL&lt;/i&gt; genotypes. We aimed to explore the association of common genetic variants of &lt;i&gt;KL&lt;/i&gt; with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; 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 &lt;i&gt;KL&lt;/i&gt; and phenotypes were analyzed through a linear mixed-effects model. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; 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, &lt;i&gt;p&lt;/i&gt; = 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, &lt;i&gt;p&lt;/i&gt; = 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, &lt;i&gt;p&lt;/i&gt; = 0.032). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Common variants of the &lt;i&gt;KL&lt;/i&gt; 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, &lt;i&gt;KL&lt;/i&gt; may be a new early intervention target for salt-sensitive hypertension.

High Dietary Salt Intake Is Associated With Histone Methylation in Salt-Sensitive Individuals

“…We selected a total of 515 subjects (aged 18–60 years) for epidemiological investigation in seven villages in rural areas of Mei County, Baoji City, Shaanxi Province in 2004. Individuals who had stage 2 hypertension, secondary hypertension, severe cardiovascular disease or diabetes mellitus, liver or renal dysfunction, alcohol abuse, or pregnancy were excluded ( 12 ). Eventually, a total of 339 subjects were included in the study and a dietary intervention trial was conducted.…”

“…Eventually, a total of 339 subjects were included in the study and a dietary intervention trial was conducted. The subjects sequentially received daily diet for 3 days, a low-salt (LS) diet (LS: 51.3 mmol/day sodium) for 7 days, a high-salt (HS) diet (307.7 mmol/day sodium) for 7 days, and a high-salt plus potassium diet (307.7 mmol/day sodium + 60 mmol/day potassium) for another 7 days ( Figure 1A ) ( 12 ). To ensure the dietary compliance, each participant was required to have their breakfast, lunch, and dinner in research kitchen with professional chefs under the supervision of staff.…”