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The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells.

Abstract：

OBJECTIVE:Obesity and cardiovascular disease recognize a common metabolic soil and may therefore share part of their genetic background. Genome-wide association studies have identified variability at the SH2B1 locus as a predictor of obesity. We investigated whether SNP rs4788102, which captures the entire SH2B1 variability, is associated with coronary artery disease (CAD) and/or myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). DESIGN AND SETTING:SNP rs4788102 was typed in 2015 White subjects with T2DM from three CAD case-control studies [n=740 from the Gargano Hearth Study (GHS, Italy); n=818 from the Joslin Hearth Study (JHS, Boston); n=457 from the University of Catanzaro (CZ, Italy)]. RESULTS:SNP rs4788102 (G/A) was not associated with CAD (overall allelic OR=1.06, 95% CI=0.93-1.21; p=0.37). On the contrary, it was associated with MI in GHS (1.42, 1.12-1.81; p=0.004) and in the three samples analyzed together (1.21, 1.04-1.41; p=0.016). Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n=4, p=0.03) but not the G/A (n=5, p=0.83) genotype. Of the SNPs in perfect LD with rs4788102, one (rs7498665) affects amino acid polarity (Ala484Thr) and falls into a highly conserved protein segment of SH2B1 containing a class II SH3 domain binding site. CONCLUSIONS:Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells. Further studies are needed to replicate this association and dissect the biology underlying this finding.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Prudente S,Morini E,Larmon J,Andreozzi F,Di Pietro N,Nigro A,Gervino EV,Mannino GC,Bacci S,Hauser TH,Bellacchio E,Formoso G,Pellegrini F,Proto V,Menzaghi C,Frittitta L,Pandolfi A,Sesti G,Doria A,Trischitta V

doi

10.1016/j.atherosclerosis.2011.08.019

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

667-72

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(11)00823-9

journal_volume

219

pub_type

杂志文章,多中心研究

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