The Klotho Variant rs36217263 Is Associated With Poor Response to Cardioselective Beta-Blocker Therapy Among Filipinos

Clin Pharmacol Ther. 2020 Jan;107(1):221-226. doi: 10.1002/cpt.1585. Epub 2019 Aug 30.

Abstract

A common drug used for hypertension among Filipinos is beta-blockers. Variable responses to beta-blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta-blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta-blockers were enrolled in an unmatched case-control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta-blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta-blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta-blockers, which may become a potential marker to aid in the management of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / pharmacology
  • Case-Control Studies
  • Female
  • Genetic Variation
  • Genotype
  • Glucuronidase / genetics*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Klotho Proteins
  • Male
  • Middle Aged
  • Philippines
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Glucuronidase
  • Klotho Proteins