The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells.
The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells.
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DOI：
10.1016/j.atherosclerosis.2011.08.019
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发表时间：
2011-12
期刊：
影响因子：
5.3
通讯作者：
Trischitta, Vincenzo
中科院分区：
文献类型：
--
作者：
Prudente, Sabrina;Morini, Eleonora;Larmon, Jay;Andreozzi, Francesco;Di Pietro, Natalia;Nigro, Angela;Gervino, Ernest V.;Mannino, Gaia Chiara;Bacci, Simonetta;Hauser, Thomas H.;Bellacchio, Emanuele;Formoso, Gloria;Pellegrini, Fabio;Proto, Vittoria;Menzaghi, Claudia;Frittitta, Lucia;Pandolfi, Assunta;Sesti, Giorgio;Doria, Alessandro;Trischitta, Vincenzo
关键词：
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). SNP rs4788102 was typed in 2,015 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)]. 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. 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.
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影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
3.7
作者：
GORFIEN, S;SPECTOR, A;WEISS, S
通讯作者：
WEISS, S
DOI：
10.1006/bbrc.1999.1116
发表时间：
1999-08-11
影响因子：
3.1
作者：
Oishi, K;Mukai, H;Ona, Y
通讯作者：
Ona, Y
影响因子：
7.7
作者：
Soccio, Teresa;Zhang, Yuan-Yuan;Doria, Alessandro
通讯作者：
Doria, Alessandro