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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, et al
The Journal of clinical endocrinology and metabolism. 2016;(7):2751-8
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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.