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

Shibao CA, Celedonio JE, Ramirez CE, Love-Gregory L, Arnold AC, Choi L, Okamoto LE, Gamboa A, Biaggioni I, Abumrad NN, Abumrad NA
J Clin Endocrinol Metab. 2016 101 (7): 2751-8

PMID: 27144937 · PMCID: PMC4929841 · DOI:10.1210/jc.2016-1294

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.

MeSH Terms (18)

Adult Cardiovascular Diseases Case-Control Studies CD36 Antigens Drug Resistance Endothelium, Vascular Female Genetic Predisposition to Disease Humans Insulin Resistance Metabolic Syndrome Middle Aged Obesity Phosphodiesterase 5 Inhibitors Polymorphism, Single Nucleotide Sildenafil Citrate Treatment Outcome Vasodilation

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