一种常见的CD36变体影响内皮功能及对磷酸二酯酶5抑制剂治疗的反应。
A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition.
作者信息
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
机构信息
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.
出版信息
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.
背景
清道夫受体CD36在体外影响内皮一氧化氮 - cGMP途径。改变CD36水平的基因变异在非裔美国人（AA）中很常见，这是一个内皮功能障碍风险很高的人群。
目的
研究编码CD36变体rs3211938（G/T）的次要等位基因（G）使CD36水平降低约50%是否会影响内皮功能、胰岛素敏感性（IS）以及对一氧化氮 - cGMP增强剂西地那非治疗的反应。
设计
在年龄和体重指数匹配的肥胖AA女性中，无论是否携带rs3211938的G等位基因，测定其IS（频繁采样静脉葡萄糖耐量）和内皮功能（血流介导的血管舒张[FMD]）（方案1）。使用随机、安慰剂对照试验（方案2），在患有代谢综合征且携带/不携带CD36变体的AA女性中测试慢性西地那非治疗对IS和FMD的影响。
地点
两中心研究。
参与者
肥胖AA女性。
干预
每日三次服用20毫克枸橼酸西地那非或安慰剂，共4周。
主要结局
IS、FMD。
结果
与非携带者相比，G等位基因携带者的FMD（P = 0.03）和cGMP水平（P = 0.01）较低。西地那非未改善IS，平均差异为0.12（95%置信区间[CI]，-0.33至0.58；P = 0.550）。然而，FMD对西地那非的反应与rs3211938之间存在显著交互作用（P = 0.018）。G携带者的FMD有改善趋势，为2.9（95%CI，-0.9至6.8；P = 0.126），而非携带者的FMD则恶化，为-2.6（95%CI，-5.1至-0.1；P = 0.04）。
结论
数据证明了一种常见基因变异对内皮功能障碍易感性及其对西地那非治疗反应的影响。
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