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Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure,

Dan E Arking1, Gil Atzmon, Albert Arking

  • 1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.

Circulation Research
|January 29, 2005
PubMed

Insights

The KL-VS gene variant offers a survival advantage in heterozygotes but increases risks for cardiovascular issues and mortality in homozygotes. This genetic factor impacts longevity, high-density lipoprotein cholesterol, and blood pressure.

Area of Science:

  • Genetics
  • Cardiovascular Disease
  • Longevity Research

Background:

  • The KL-VS allele, a functional variant of KLOTHO, has been linked to aging and early coronary artery disease.
  • Previous studies suggested an association between KL-VS and human aging.

Purpose of the Study:

  • To investigate the influence of the KL-VS allele on cardiovascular disease risk factors.
  • To determine the impact of KL-VS on cardiovascular events and mortality.
  • To analyze the role of KL-VS in longevity across different populations.

Main Methods:

  • Genotyping of 525 Ashkenazi Jews (216 probands aged >=95, 309 controls aged 51-94) for the KL-VS allele.
  • Multivariate regression analysis to assess cardiovascular risk factors (HDL-C, SBP).
  • Logistic and Cox regression analyses to evaluate the association of KL-VS with vascular events and mortality.

Main Results:

  • A heterozygous advantage for longevity was observed in individuals aged >=79 (P<0.004).
  • KL-VS genotype was associated with high-density lipoprotein cholesterol (HDL-C) and systolic blood pressure (SBP).
  • Heterozygous KL-VS individuals had lower stroke risk, while homozygous KL-VS individuals had higher stroke and mortality risk compared to wild-type.

Conclusions:

  • The KL-VS allele confers a heterozygous advantage for longevity.
  • A homozygous disadvantage for KL-VS is associated with adverse cardiovascular outcomes, including lower HDL-C, higher SBP, and increased stroke and mortality risk.
  • The KL-VS allele plays a significant role in a genetic model influencing cardiovascular health and lifespan.

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