PMID- 27005817
OWN - NLM
STAT- MEDLINE
DCOM- 20161011
LR  - 20220318
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 15
DP  - 2016 Mar 22
TI  - Association between insulin receptor substrate-1 polymorphisms and high platelet 
      reactivity with clopidogrel therapy in coronary artery disease patients with type 
      2 diabetes mellitus.
PG  - 50
LID - 10.1186/s12933-016-0362-0 [doi]
LID - 50
AB  - BACKGROUND: The mechanisms leading to the high on-treatment platelet reactivity 
      in diabetes patients are not fully elucidated. The genetic factors may be 
      associated with the diminished antiplatelet efficacy of dual antiplatelet 
      therapy. We investigated the possible association between insulin receptor 
      substrate-1 (IRS-1) polymorphisms and high platelet reactivity in coronary artery 
      disease (CAD) patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 
      674 CAD patients with T2DM were enrolled in this study. Platelet aggregation and 
      platelet activation were assessed with light transmission aggregometry and flow 
      cytometry analysis, respectively. Participants were divided into high platelet 
      reactivity (HPR) group and non-HPR group according to their maximal platelet 
      aggregation. Genotypes were identified by polymerase chain reaction and direct 
      sequencing of genomic DNA. The association between IRS-1 genetic variants and 
      platelet function was assessed. RESULTS: There were 233 participants in the HPR 
      group and 441 participants in the non-HPR group. G allele frequencies of 
      rs13431554 were 27.7 % for the HPR group and 18.6 % for the non-HPR group (p < 
      0.001). Adenosine diphosphate and arachidonic acid induced platelet aggregation 
      were significantly higher in G allele carriers compared with non-carriers (56.8 +/- 
      16.2 vs 52.0 +/- 17.9 %, p < 0.01, 28.9 +/- 18.6 vs 25.2 +/- 17.8 %, p < 0.01, 
      respectively). We observed that P-selectin expression and PAC-1 binding were 
      higher in G allele carriers compared with non-carriers (40.8 +/- 12.4 vs 36.2 +/- 
      13.8, p = 0.01; 43.7 +/- 15.9 vs 38.7 +/- 19.9, p = 0.03, respectively). CONCLUSION: 
      The G allele of rs13431554 in the IRS-1 gene was associated with a hyperreactive 
      platelet phenotype in the CAD patients with T2DM.
FAU - Zhang, Dingyu
AU  - Zhang D
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Zhang, Xiaolin
AU  - Zhang X
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Liu, Dan
AU  - Liu D
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Liu, Tengfei
AU  - Liu T
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Cai, Wenzhi
AU  - Cai W
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Yan, Chenghui
AU  - Yan C
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China.
FAU - Han, Yaling
AU  - Han Y
AD  - Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern 
      Hospital, 83 Wenhua Road, Shenyang, 110840, China. hanyaling@263.net.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160322
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (P-Selectin)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (SELP protein, human)
RN  - A74586SNO7 (Clopidogrel)
RN  - OM90ZUW7M1 (Ticlopidine)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aged
MH  - Aspirin/therapeutic use
MH  - Blood Platelets/*drug effects/metabolism
MH  - Clopidogrel
MH  - Coronary Artery Disease/blood/diagnosis/genetics/*therapy
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*genetics
MH  - Drug Resistance
MH  - Drug Therapy, Combination
MH  - Female
MH  - Flow Cytometry
MH  - Gene Frequency
MH  - Haplotypes
MH  - Humans
MH  - Insulin Receptor Substrate Proteins/*genetics
MH  - Male
MH  - Middle Aged
MH  - P-Selectin/blood
MH  - *Percutaneous Coronary Intervention/adverse effects
MH  - Pharmacogenetics
MH  - Phenotype
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/adverse effects/*therapeutic use
MH  - Platelet Function Tests
MH  - *Polymorphism, Single Nucleotide
MH  - Ticlopidine/adverse effects/*analogs & derivatives/therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC4804508
OTO - NOTNLM
OT  - Clopidogrel
OT  - Coronary artery disease
OT  - High platelet reactivity
OT  - Insulin receptor substrate-1
OT  - Single nucleotide polymorphism
OT  - Type 2 diabetes mellitus
EDAT- 2016/03/24 06:00
MHDA- 2016/10/12 06:00
PMCR- 2016/03/22
CRDT- 2016/03/24 06:00
PHST- 2015/10/28 00:00 [received]
PHST- 2016/03/03 00:00 [accepted]
PHST- 2016/03/24 06:00 [entrez]
PHST- 2016/03/24 06:00 [pubmed]
PHST- 2016/10/12 06:00 [medline]
PHST- 2016/03/22 00:00 [pmc-release]
AID - 10.1186/s12933-016-0362-0 [pii]
AID - 362 [pii]
AID - 10.1186/s12933-016-0362-0 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2016 Mar 22;15:50. doi: 10.1186/s12933-016-0362-0.