The concomitant presence of polymorphic alleles of interleukin-1beta, interleukin-6 and apolipoprotein E is associated with an increased risk of myocardial infarction in elderly men. Results from a pilot study.
Genetic background of inflammatory or anti-inflammatory molecules may be helpful in identifying subjects with increased or decrease risk of developing cardiovascular disease. Bi-allele polymorphism (C > T) in the promoter region (-511) of the interleukin-1beta (IL-1beta) gene and the bi-allele polymorphism (G > C) in the promoter region (-174) of interleukin-6 (IL-6) gene were determined in elderly men patients with myocardial infarction (MI) and healthy controls. Each subject was also genotyped for the triallelic polymorphism of the apolipoprotein E epsilon gene. The IL-6C and APOE epsilon4 alleles were independently associated with a mild or moderate increased risk of MI, whilst the allele C of the IL-1beta was not independently linked to MI risk. However, the simultaneous presence of the allele C of IL-1beta, the allele C of IL-6 and epsilon4 allele of APOE was strongly associated with the disease. Data from this cross-sectional study suggest that the functional interaction of these three genes affects pathogenetic mechanisms of MI and an impaired regulation of immune responses plays a pivotal role in the disease. Furthermore, genetic background of inflammatory genes may influence longevity of human species by affecting inflammatory responses associated to cardiovascular diseases. The administration of anti-inflammatory compounds to middle age healthy subjects with increased genetic susceptibility of developing MI might decrease the incidence and prevalence of cardiovascular events in aging.
Licastro
Federico
F
Department of Experimental Pathology, Via S. Giacomo 14, 40126 Bologna, Italy. licastro@alma.unibo.it
Chiappelli
Martina
M
Caldarera
Claudio Marcello
CM
Tampieri
Cecilia
C
Nanni
Samuele
S
Gallina
Margherita
M
Branzi
Angelo
A
D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk
D001057:Apolipoproteins E; D007375:Interleukin-1; D015850:Interleukin-6