A potential pharmacogenomic strategy for anticoagulant treatment in non-ST elevation acute coronary syndromes: the role of interleukin-1 receptor antagonist genotype.
OBJECTIVE
Our aim was to determine a pharmacogenomic approach to heparin use in non-ST elevation acute coronary syndromes, specifically the impact of interleukin (IL)-1 receptor antagonist polymorphisms upon von Willebrand factor (vWF) responses to unfractionated heparin (UFH) and low molecular weight heparin (LMWH).


BACKGROUND
In acute coronary syndromes (ACS), identification of specific biological or genetic targets to direct pharmacological treatment remains a challenge. vWF has been shown to predict future cardiovascular risk and the response to anticoagulant treatments during non-ST elevation ACS. IL-1 receptor antagonist (IL-1RN) polymorphisms predict the change in vWF between 24 and 48 h (Delta vWF) during non-ST elevation ACS.


METHODS
We genotyped at the IL-1 locus, 67 patients with non-ST elevation ACS who received either LMWH or UFH, and measured vWF levels at 24 and 48 h.


RESULTS
LMWH was superior to UFH in reducing the rise in vWF between 24 and 48 h in the cohort as a whole. However, when patients were stratified by IL-1RN genotype, LMWH was superior to UFH in reducing Delta vWF only in allele *2 carriers (0.51 iU mL(-1) vs. 1.37, P < 0.01), but not in non-carriers (- 0.03 iU mL(-1) vs. 0.15, P = NS).


CONCLUSIONS
IL-1RN genotype may be a useful marker to identify patients that benefit from LMWH in non-ST elevation ACS.
Ray
K K
KK
Cardiovascular Research Unit, Clinical Sciences Centre North, Northern General Hospital, Sheffield, UK. kkray@partners.org
Francis
S
S
Crossman
D C
DC
D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis / Q000187:drug effects
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D014841:von Willebrand Factor; D006493:Heparin