A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition

J Clin Endocrinol Metab. 2016 Jul;101(7):2751-8. doi: 10.1210/jc.2016-1294. Epub 2016 May 4.


Context: The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction.

Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences endothelial function, insulin sensitivity (IS), and the response to treatment with the nitric oxide-cGMP potentiator sildenafil.

Design: IS (frequently sampled iv glucose tolerance) and endothelial function (flow mediated dilation [FMD]) were determined in age- and body mass index-matched obese AA women with or without the G allele of rs3211938 (protocol 1). Effect of chronic sildenafil treatment on IS and FMD was tested in AA women with metabolic syndrome and with/without the CD36 variant, using a randomized, placebo-controlled trial (protocol 2).

Setting: Two-center study.

Participants: Obese AA women.

Intervention: A total of 20-mg sildenafil citrate or placebo thrice daily for 4 weeks.

Main outcome: IS, FMD.

Results: G allele carriers have lower FMD (P = .03) and cGMP levels (P = .01) than noncarriers. Sildenafil did not improve IS, mean difference 0.12 (95% confidence interval [CI], -0.33 to 0.58; P = .550). However, there was a significant interaction between FMD response to sildenafil and rs3211938 (P = .018). FMD tended to improve in G carriers, 2.9 (95% CI, -0.9 to 6.8; P = .126), whereas it deteriorated in noncarriers, -2.6 (95% CI, -5.1 to -0.1; P = .04).

Conclusions: The data document influence of a common genetic variant on susceptibility to endothelial dysfunction and its response to sildenafil treatment.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD36 Antigens / genetics*
  • Cardiovascular Diseases / genetics
  • Case-Control Studies
  • Drug Resistance / genetics
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Insulin Resistance / genetics
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / genetics
  • Obesity / physiopathology
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Sildenafil Citrate / therapeutic use*
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vasodilation / genetics


  • CD36 Antigens
  • Phosphodiesterase 5 Inhibitors
  • Sildenafil Citrate