کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5947951 1172375 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance
ترجمه فارسی عنوان
اثر مشترک ژن های سیگنالینگ انسولین در حوادث قلبی عروقی و مقاومت کلی انسولین بدن و اندوتلیال
کلمات کلیدی
حساسیت ژنتیکی، پلیمورفیسم نامشخص، حساسیت به انسولین، عملکرد اندوتلیال وابسته به انسولین،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی

ObjectiveInsulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity.Design and setting1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction-MI, stroke and cardiovascular death) in 733 patients (2186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose <126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs).Results1. Risk variants jointly predicted cardiovascular events (HR = 1.181; p = 0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p = 0.006). 3. A significant association was also observed with ISI (p = 0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p = 0.009).ConclusionsInsulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies.

► Combined role of three SNPs in insulin signaling genes on CVD has been investigated. ► Findings show a combined effect of the SNPs in predicting major cardiovascular events. ► Findings have been replicated in a cross-sectional study on age at MI. ► The role of the three SNPs has been evaluated on whole body insulin resistance. ► Insulin-stimulated NOS activity in HUVECs according to SNPs genotype has been evaluated.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 226, Issue 1, January 2013, Pages 140-145
نویسندگان
, , , , , , , , , , , , , ,