PMID- 21907990
OWN - NLM
STAT- MEDLINE
DCOM- 20120405
LR  - 20211020
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 219
IP  - 2
DP  - 2011 Dec
TI  - The SH2B1 obesity locus is associated with myocardial infarction in diabetic 
      patients and with NO synthase activity in endothelial cells.
PG  - 667-72
LID - 10.1016/j.atherosclerosis.2011.08.019 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Prudente, Sabrina
AU  - Prudente S
AD  - IRCSS Casa Sollievo della Sofferenza-Mendel Laboratory, San Giovanni Rotondo, 
      Italy. s.prudente@css-mendel.it
FAU - Morini, Eleonora
AU  - Morini E
FAU - Larmon, Jay
AU  - Larmon J
FAU - Andreozzi, Francesco
AU  - Andreozzi F
FAU - Di Pietro, Natalia
AU  - Di Pietro N
FAU - Nigro, Angela
AU  - Nigro A
FAU - Gervino, Ernest V
AU  - Gervino EV
FAU - Mannino, Gaia Chiara
AU  - Mannino GC
FAU - Bacci, Simonetta
AU  - Bacci S
FAU - Hauser, Thomas H
AU  - Hauser TH
FAU - Bellacchio, Emanuele
AU  - Bellacchio E
FAU - Formoso, Gloria
AU  - Formoso G
FAU - Pellegrini, Fabio
AU  - Pellegrini F
FAU - Proto, Vittoria
AU  - Proto V
FAU - Menzaghi, Claudia
AU  - Menzaghi C
FAU - Frittitta, Lucia
AU  - Frittitta L
FAU - Pandolfi, Assunta
AU  - Pandolfi A
FAU - Sesti, Giorgio
AU  - Sesti G
FAU - Doria, Alessandro
AU  - Doria A
FAU - Trischitta, Vincenzo
AU  - Trischitta V
LA  - eng
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
GR  - R01 HL073168/HL/NHLBI NIH HHS/United States
GR  - HL73168/HL/NHLBI NIH HHS/United States
GR  - DK36836/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110819
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Insulin)
RN  - 0 (SH2B1 protein, human)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Aged
MH  - Boston
MH  - Case-Control Studies
MH  - Computational Biology
MH  - Coronary Artery Disease/enzymology/genetics
MH  - Diabetes Complications/enzymology/*genetics
MH  - Diabetes Mellitus, Type 2/complications/enzymology/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Human Umbilical Vein Endothelial Cells/*enzymology
MH  - Humans
MH  - Insulin/metabolism
MH  - Italy
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/enzymology/*genetics
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Obesity/*genetics
MH  - Odds Ratio
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Risk Assessment
MH  - Risk Factors
PMC - PMC3728428
MID - NIHMS490069
COIS- DUALITY OF INTEREST The authors declare that there is no duality of interest 
      associated with this manuscript.
EDAT- 2011/09/13 06:00
MHDA- 2012/04/06 06:00
PMCR- 2013/07/31
CRDT- 2011/09/13 06:00
PHST- 2011/06/22 00:00 [received]
PHST- 2011/07/22 00:00 [revised]
PHST- 2011/08/06 00:00 [accepted]
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/04/06 06:00 [medline]
PHST- 2013/07/31 00:00 [pmc-release]
AID - S0021-9150(11)00823-9 [pii]
AID - 10.1016/j.atherosclerosis.2011.08.019 [doi]
PST - ppublish
SO  - Atherosclerosis. 2011 Dec;219(2):667-72. doi: 
      10.1016/j.atherosclerosis.2011.08.019. Epub 2011 Aug 19.