Method of identifying and treating a person having a predisposition to or afflicted with a cardiometabolic disease
The invention relates to method for identifying and selecting a subject with increased risk of developing a cardiometabolic disease and optionally, providing a personalized medicine method, which may involve sequencing at least part of a genome of one or more cells in a blood sample of the subject and identifying from said sequencing one or more mutations in one or more somatic mutations.
1. A method of treating or preventing coronary heart disease (CHD) in a human subject, comprising the steps of:
(a) sequencing at least part of a genome of one or more cells in a blood sample of the subject, wherein the at least part of said genome comprises a DNMT3A gene,
(b) detecting a loss of function mutation in the DNMT3A gene selected from a frameshift mutation and a nonsense mutation; and
(c) administering a lipid modifying medicine to the subject.
2. The method according to claim 1 , wherein the presence of said mutation indicates an increase in red blood cell distribution width (RDW).
3. The method according to claim 1 , wherein the subject has CHD.
4. The method according to claim 1 , wherein the one more cells in the blood sample are hematopoietic stem cells (HSCs), committed myeloid progenitor cells having long term self-renewal capacity or mature lymphoid cells having long term self-renewal capacity.
5. The method according to claim 1 , wherein the part of the genome is an exome.
6. The method according to claim 1 , wherein the sequencing is whole exome sequencing (WES).
7. The method according to claim 1 , wherein the subject also exhibits one or more risk factors of being a smoker, having a high level of total cholesterol or having high level of high-density lipoprotein (HDL).
8. The method of claim 1 , wherein the lipid-modifying medicine is a statin.
9. The method of claim 1 , wherein the lipid-modifying medicine is a PCSK9 inhibitor.
10. The method of claim 9 , wherein the PCSK9 inhibitor is a monoclonal antibody.
11. A method for providing personalized medicine to a human subject with increased risk of CHD, said method comprising the steps of
(a) sequencing at least part of a genome of one or more cells in a blood sample of the subject, wherein the at least part of the genome comprises a DMNT3A gene,
(b) detecting a loss of function-mutation in the DNMT3A gene selected from a frameshift mutation and a nonsense mutation; and
(c) administering a lipid-modifying medicine to the subject.
12. The method according to claim 11 , wherein the subject has CHD.
13. The method according to claim 11 , wherein the one more cells in the blood sample are hematopoietic stem cells (HSCs), committed myeloid progenitor cells having long term self-renewal capacity or mature lymphoid cells having long term self-renewal capacity.
14. The method according to claim 11 , wherein the part of the genome is an exome.
15. The method according to claim 11 , wherein the sequencing is whole exome sequencing (WES).
16. The method according to claim 11 , wherein the subject also exhibits one or more risk factors of being a smoker, having a high level of total cholesterol or having high level of high-density lipoprotein (HDL).
17. The method of claim 11 , wherein the lipid-modifying medicine is a statin.
18. The method of claim 11 , wherein the lipid-modifying medicine is a PCSK9 inhibitor.
19. The method of claim 18 , wherein the PCSK9 inhibitor is a monoclonal antibody.
20. A method of treating or preventing coronary heart disease (CHD) in a human subject, wherein the genome of a blood cell in said subject comprises a loss of function mutation in a DNMT3A gene selected from a frameshift mutation and a nonsense mutation, the method comprising administering a lipid-modifying medicine to the subject.
21. The method of claim 20 , wherein the lipid-modifying medicine is a statin.
22. The method of claim 20 , wherein the lipid-modifying medicine is a PCSK9 inhibitor.
23. The method of claim 22 , wherein the PCSK9 inhibitor is a monoclonal antibody.