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

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

Author information

1
Department of Medicine (C.A.S., J.E.C., C.E.R., A.C.A., L.E.O., A.G., I.B.), Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232; Department of Medicine (L.L.-G., N.A.A.), Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri 63110; Department of Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Department of Surgery (N.N.A.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

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.

PMID:
27144937
PMCID:
PMC4929841
DOI:
10.1210/jc.2016-1294
[Indexed for MEDLINE]
Free PMC Article

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