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抵抗素基因启动子-420C/G变异对代谢综合征、肥胖症、心肌梗死及肾功能障碍的影响。

Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction.

作者信息

Norata G D, Ongari M, Garlaschelli K, Tibolla G, Grigore L, Raselli S, Vettoretti S, Baragetti I, Noto D, Cefalù A B, Buccianti G, Averna M, Catapano A L

机构信息

Department of Pharmacological Sciences, University of Milan, Milan, Italy.

出版信息

J Intern Med. 2007 Jul;262(1):104-12. doi: 10.1111/j.1365-2796.2007.01787.x.

Abstract

OBJECTIVE

Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (-420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease.

DESIGN AND RESULTS

First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele.

CONCLUSION

Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls.

摘要

目的

抵抗素是一种脂肪因子,有人认为它与炎症标志物相关,并可预测人类冠状动脉粥样硬化和II型糖尿病。抵抗素启动子区常见的单核苷酸多态性(SNP)(-420C/G)与抵抗素血浆水平升高及II型糖尿病易感性相关。本研究旨在探讨-420C/G多态性与代谢综合征、肥胖、心肌梗死和肾脏疾病之间的关联。

设计与结果

首先,我们研究了PLIC研究(一项基于人群的队列研究)中的1542名受试者。根据弗雷明汉算法,GG携带者肥胖和代谢综合征的患病率更高,血浆甘油三酯水平、体重指数、收缩压和舒张压以及心血管风险也有所增加(所有P<0.05)。接下来,我们在一项病例对照研究中调查了-420C/G抵抗素多态性的存在情况,该研究包括300名心肌梗死患者和300名年龄和性别匹配的对照,然后我们研究了-420C/G SNP在88例轻至中度肾功能不全患者中的作用。在PLIC研究、心肌梗死(MI)病例和肾功能不全患者之间,未观察到等位基因频率有统计学显著差异。外周血单个核细胞的促炎基因表达谱分析未发现野生型受试者与罕见等位基因携带者之间有任何差异。

结论

我们的数据表明,抵抗素基因-420C/G SNP的存在与肥胖和代谢综合征增加有关,尽管与对照组相比,在高心血管风险受试者(如心肌梗死患者或肾功能不全患者)中该SNP并无差异。

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