Cumulative burden of atherosclerotic risk genotypes and the age at onset of a first myocardial infarction: a case-only carriership approach.
BACKGROUND
Previously identified atherosclerotic genetic factors have been studied mostly in case-control studies and in nonuniform ethnic populations, whereas data on the cumulative contribution of genetic factors to an earlier onset of a first myocardial infarction (MI) are limited. We hypothesized that several genetic atherosclerotic single nucleotide polymorphisms (SNPs) may exert an additive effect on the earlier occurrence of coronary atherothrombotic disease after adjustment for clinical factors.


METHODS
Eighteen atherosclerotic high-risk SNPs were selected based upon meta-analyses of 614 published reports, and were incorporated into a carriership model. Multivariate regression analysis was used to identify the independent contribution of selected genotypes to the age at onset of a first MI in a cohort of 814 white (n = 622) and nonwhite (n = 192) patients enrolled in the Thrombogenic Factors and Coronary Events Study.


RESULTS
The analysis demonstrated that selected genotypes were significantly associated with an earlier occurrence of a first MI among white patients (an average of 0.6 year reduction per carried genotype; P = 0.027), whereas the contribution of genotypes to MI onset among nonwhite patients was not significant (an average of 0.7 year increase per carried genotype; P = 0.16), with a significant ethnic x genotype interaction effect (P = 0.02).


CONCLUSIONS
Our findings suggest that currently identified atherosclerotic genetic factors confer an independent additive contribution to the earlier onset of coronary atherothrombotic disease among white patients. The lack of a significant association between these genotypes and outcome in other ethnic groups suggests that cardiovascular genetic risk should be studied directly in these populations.
Goldenberg
Ilan
I
Cardiology Unit of the Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. Ilan.Goldenberg@heart.rochester.edu
Moss
Arthur J
AJ
Ryan
Daniel
D
Pietrasik
Grzegorz
G
Zareba
Wojciech
W
McNitt
Scott
S
Eberly
Shirley W
SW
D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D012044:Regression Analysis; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D044465:White People / Q000235:genetics