Diagnostic markers for platelet function and methods of use
Disclosed herein are biomarkers of platelet function and methods for assessing platelet function in response to anti-platelet therapy and for determining a prognosis, diagnosis, or risk identification in a patient by detecting at least one biomarker of platelet function in the patient as well as determining amounts thereof. The biomarkers may be used to identify a patient as a candidate for treatment with an antiplatelet agent and to monitor and adjust antiplatelet therapy in a patient.
1. A method for determining risk of death and/or myocardial infarction in a human subject, the method comprising:
(a) obtaining a blood sample from the subject;
(b) determining the gene expression level of at least one biomarker of platelet function selected from the group consisting of ALOX12, ARHGAP18, C12orf39, CALD1, CLEC1B, CLEC4D, CLU, CMTM5, CTDSPL, ELOVL7, ENDOD1, FRMD3, FSTL1, GNG11, GP1BB, HIST1H2AG, HIST1H2BG, HIST1H3H, IGF2BP3, ITGA2B, ITGB3, LGALSL, MGLL, MYL9, PARVB, PBX1, PCGF5, PCSK6, PDE5A, PF4, PPBP, PRKAR2B, PROS1, SELP, SH3BGRL2, SLC24A3, SPARC, TGFB1I1, THBS1, TPM1, TREML1, TTC7B, and TUBB1 in the blood sample from the subject, wherein the gene expression level is determined by measuring the mRNA level;
(c) identifying the subject as being at risk of death and/or myocardial infarction when the gene expression level of the at least one biomarker of platelet function in the sample is greater than the reference level of the at least one biomarker of platelet function,
wherein the reference level is the level of the at least one biomarker of platelet function in a healthy subject, or a subject without cardiovascular disease, or a subject having cardiovascular disease but who has not suffered death or myocardial infarction; and
(d) administering an antiplatelet agent to the subject identified as being at risk of death and/or myocardial infarction.
2. The method of claim 1 , wherein the reference level of the at least one biomarker of platelet function is the cutoff value of the at least one biomarker of platelet function determined by measuring a change in gene expression levels between blood samples obtained before and after aspirin treatment of a healthy patient group or patients without cardiovascular disease.
3. The method of claim 1 , wherein the at least one biomarker of platelet function is selected from the group consisting of C12orf39, CLEC4D, CLU, ENDOD1, FRMD3, GP1BB, HIST1H2BG, HIST1H3H, IGF2BP3, ITGA2B, MYL9, PBX1, PCGF5, PPBP, PRKAR2B, PROS1, SELP, SH3BGRL2, TGFB1I1, THBS1, TPM1, TREML1, and TTC7B.
4. The method of claim 1 , wherein the at least one biomarker of platelet function is selected from the group consisting of ITGA2B, ENDOD1, PBX1, LGALSL, TPM1, ITGB3, THBS1, HIST1H3H, and FRMD3.