A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition

Cyndya A. Shibao, Jorge E. Celedonio, Claudia E. Ramirez, Latisha Love-Gregory, Amy C. Arnold, Leena Choi, Luis E. Okamoto, Alfredo Gamboa, Italo Biaggioni, Naji N. Abumrad, Nada A. Abumrad

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2751-2758
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number7
DOIs
StatePublished - Jul 2016

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Type 5 Cyclic Nucleotide Phosphodiesterases
Dilatation
Insulin Resistance
African Americans
Insulin
Alleles
Confidence Intervals
Nitric Oxide
Therapeutics
Placebos
Flow interactions
Scavenger Receptors
Clinical Protocols
Sildenafil Citrate
Body Mass Index
Randomized Controlled Trials
Glucose

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Shibao, Cyndya A. ; Celedonio, Jorge E. ; Ramirez, Claudia E. ; Love-Gregory, Latisha ; Arnold, Amy C. ; Choi, Leena ; Okamoto, Luis E. ; Gamboa, Alfredo ; Biaggioni, Italo ; Abumrad, Naji N. ; Abumrad, Nada A. / A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 7. pp. 2751-2758.
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title = "A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition",
abstract = "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.",
author = "Shibao, {Cyndya A.} and Celedonio, {Jorge E.} and Ramirez, {Claudia E.} and Latisha Love-Gregory and Arnold, {Amy C.} and Leena Choi and Okamoto, {Luis E.} and Alfredo Gamboa and Italo Biaggioni and Abumrad, {Naji N.} and Abumrad, {Nada A.}",
year = "2016",
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Shibao, CA, Celedonio, JE, Ramirez, CE, Love-Gregory, L, Arnold, AC, Choi, L, Okamoto, LE, Gamboa, A, Biaggioni, I, Abumrad, NN & Abumrad, NA 2016, 'A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 7, pp. 2751-2758. https://doi.org/10.1210/jc.2016-1294

A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition. / Shibao, Cyndya A.; Celedonio, Jorge E.; Ramirez, Claudia E.; Love-Gregory, Latisha; Arnold, Amy C.; Choi, Leena; Okamoto, Luis E.; Gamboa, Alfredo; Biaggioni, Italo; Abumrad, Naji N.; Abumrad, Nada A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 7, 07.2016, p. 2751-2758.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A common CD36 variant influences endothelial function and response to treatment with phosphodiesterase 5 inhibition

AU - Shibao, Cyndya A.

AU - Celedonio, Jorge E.

AU - Ramirez, Claudia E.

AU - Love-Gregory, Latisha

AU - Arnold, Amy C.

AU - Choi, Leena

AU - Okamoto, Luis E.

AU - Gamboa, Alfredo

AU - Biaggioni, Italo

AU - Abumrad, Naji N.

AU - Abumrad, Nada A.

PY - 2016/7

Y1 - 2016/7

N2 - 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.

AB - 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.

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