Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years.
BACKGROUND
Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined.


METHODS
Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus).


RESULTS
In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI.


CONCLUSIONS
Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.
Ortlepp
Jan R
JR
Medical Clinic I, University Hospital of Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. jrortlepp@ukaachen.de
Krantz
Constanze
C
Kimmel
Melanie
M
von Korff
Alexei
A
Vesper
Katharina
K
Schmitz
Fabian
F
Mevissen
Vera
V
Janssens
Uwe
U
Franke
Andreas
A
Hanrath
Peter
P
Zerres
Klaus
K
Hoffmann
Rainer
R
D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D054390:Receptors, CCR2; D018167:Receptors, Calcitriol / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D012307:Risk Factors
C515334:CCR2 protein, human; D015850:Interleukin-6; D054390:Receptors, CCR2; D018167:Receptors, Calcitriol; D019707:Receptors, Chemokine