Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach.
OBJECTIVE
Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic-epidemiological data are available.


METHODS
Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs).


RESULTS
Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR=0.455, 95% CI=0.215-0.960, uncorrected p=0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation.


CONCLUSIONS
In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders.
Zee
Robert Y L
RY
Center for Cardiovascular Disease Prevention, The Donald W. Reynolds Center for Cardiovascular Research, The Leducq Center for Molecular and Genetic Epidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 022215, USA. rzee@rics.bwh.harvard.edu
Hennessey
Hooman
H
Michaud
Sherri E
SE
Ridker
Paul M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta