Abstract
BackgroundThe 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).MethodsA 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.ResultsThere 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).ConclusionThe G allele of rs13431554 in the IRS-1 gene was associated with a hyperreactive platelet phenotype in the CAD patients with T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0362-0) contains supplementary material, which is available to authorized users.
Highlights
The mechanisms leading to the high on-treatment platelet reactivity in diabetes patients are not fully elucidated
high platelet reactivity (HPR) was defined as the 75th percentile of adenosine diphosphate (ADP)-induced platelet aggregation (ADP-induced platelet aggregation >65.8 %)
This study suggested that insulin receptor substrate-1 (IRS-1) polymorphism has an effect on platelet response to dual-antiplatelet therapy in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM)
Summary
The mechanisms leading to the high on-treatment platelet reactivity in diabetes patients are not fully elucidated. 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). Marin F, et al demonstrated that single nucleotide polymorphisms (SNPs) were able to explain the variability in antiplatelet agents inefficacy [11]. Whether this may explain the heterogeneity of dual-antiplatelet therapy response in type 2 diabetes mellitus (T2DM) patients remains unexplored. Whether there is other SNP in IRS-1 related to HPR in coronary artery disease (CAD) and T2DM patients remains to be elucidated
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.