Polymorphism in the Apo(a) gene predict responsiveness to acetylsalicylic acid treatment
View Patent ↗This invention relates to nucleotide polymorphisms in the human Apo(a) gene and to the use of Apo(a) nucleotide polymorphisms in identifying whether a human subject will respond or not to treatment with acetylsalicylic acid.
1. A method for evaluating a woman's responsiveness to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event, said method comprising:
(a) genotyping nucleic acid in a sample from said woman for single nucleotide polymorphism rs3798220 at position chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1) in the apolipoprotein (a) (Apo(a)) gene;
(b) detecting a cytosine (C) or guanine(G) at said polymorphism rs3798220; and
(c) identifying the woman with a cytosine (C) or guanine(G) at rs3798220 as responsive to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event.
2. The method of claim 1 , further comprising determining a level of Lipoprotein(a) (Lp(a)) in a blood sample from the woman.
3. The method of claim 1 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 10 mg/dl or higher in a blood sample from the woman.
4. The method of claim 1 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 15 mg/dl or higher in a blood sample from the woman.
5. The method of claim 1 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 20 mg/dl or higher in a blood sample from the woman.
6. The method of claim 1 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 25 mg/dl or higher in a blood sample from the woman.
7. A method for evaluating a woman's non-responsiveness to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event, said method comprising:
(a) genotyping nucleic acid in a sample from said woman for single nucleotide polymorphism rs3798220 at position chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1) in the apolipoprotein (a) (Apo(a)) gene;
(b) detecting an adenine(A) or thymine (T) at rs3798220; and
(c) identifying the woman with an adenine(A) or thymine (T) at rs3798220 as non-responsive to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event.
8. The method of claim 1 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis.
9. The method of claim 7 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis.
10. A method for treating a woman the method comprising:
(a) genotyping nucleic acid in a sample from said woman for single nucleotide polymorphism rs3798220 at position chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1) in the apolipoprotein (a) (Apo(a)) gene;
(b) detecting a cytosine (C) or guanine(G) at rs3798220;
(c) identifying the woman with a cytosine (C) or guanine(G) at rs3798220 as likely to have responsiveness to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event; and
(d) treating the identified woman with acetylsalicylic acid to reduce the risk of a future cardiovascular event.
11. The method of claim 10 , wherein the human subject also has an elevated level of Lipoprotein(a) (Lp(a)) in the blood.
12. The method of claim 10 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 10 mg/dl or higher in a blood sample from the woman.
13. The method of claim 10 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis.
14. The method of claim 10 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 15 mg/dl or higher in a blood sample from the woman.
15. The method of claim 10 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 20 mg/dl or higher in a blood sample from the woman.
16. The method of claim 10 , wherein the woman has a level of Lipoprotein(a) (Lp(a)) about 25 mg/dl or higher in the blood sample from the woman.
17. A method for treating a woman the method comprising:
(a) genotyping nucleic acid in a sample from said woman for single nucleotide polymorphism rs3798220 at position chromosome 6:160880877 (March 2006 assembly—NCBI build 36.1) in the apolipoprotein (a) (Apo(a)) gene;
(b) detecting an adenine(A) or thymine (T) at rs3798220;
(c) identifying the woman with an adenine(A) or thymine (T) at rs3798220 as non-responsive to acetylsalicylic acid treatment to reduce the risk of a future cardiovascular event; and
(d) treating the identified woman with an anti-platelet agent or an antithrombotic agent other than acetylsalicylic acid to reduce the risk of a future cardiovascular event.
18. The method of claim 17 , wherein the antithrombotic agent is a thienopyridine or a thienopyridine derivative.
19. The method of claim 18 , the thienopyridine or thienopyridine derivative is clopidogrel, clopidogrel bisulfate, ticlopidine, prasugrel (CS-747, or LY 640315), SR 25989, or PCR 4099.
20. The method of claim 17 , wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, myocardial ischemia, chronic stable angina pectoris, unstable angina pectoris, cardiovascular death, coronary re-stenosis, coronary stent re-stenosis, coronary stent re-thrombosis, revascularization, angioplasty, transient ischemic attack, pulmonary embolism, vascular occlusion, or venous thrombosis.
21. The method of claim 17 , wherein the antithrombotic agent is cenoxaparin sodium, ximelagatran, abciximab or tirofiban.