Role of proinflammatory alleles in longevity and atherosclerosis: results of studies performed on -1562C/T MMP-9 in centenarians and myocardial infarction patients from Sicily

Abstract

Centenarians are characterized by marked delay or escape from age-associated diseases that cause mortality at earlier ages. Jointly, atherosclerosis and its complications, such as myocardial infarction (AMI), significantly contribute to mortality in the elderly. Inflammation is a key component of atherosclerosis and inflammatory genes are good candidates for the risk of the development of atherosclerosis. Genetic traits contribute to the risk of AMI and allelic variations in inflammatory genes should boost the risk of disease. If proinflammatory genotypes significantly contribute to the risk of AMI, alleles associated with disease susceptibility should not be included in the genetic background favoring longevity. Hence, genotypes of natural immunity should play an opposite role in atherosclerosis and longevity. Metalloproteinase (MMPs) are involved in tissue remodeling and therefore play a remarkable role in inflammation-based disease. MMPs are a family of Zn(2+)-dependent enzymes with proteolytic activity against connective tissue proteins such as collagens, proteoglycans, and elastin, which appear to play important roles in the development and progression of the atherosclerotic lesion. There is evidence indicating a role played by the MMPs in the weakening of atherosclerotic plaque which predisposes to lesion disruption. In this study we performed a genetic study on -1562C/T MMP-9 single nucleotide polymorphism (SNP) in order to discern a possible role in AMI. We analyzed the distribution of this SNP in 115 AMI patients, 123 controls, and 34 centenarians from Sicily. We found no significant differences in the genetic distribution and allelic frequency of -1562C/T MMP-9 SNP between the studied groups. The present results are not in agreement with our previous findings, strengthening our hypothesis that genetic background protection against cardiovascular disease is a relevant component of the longevity trait, at least in the generation of Italian male centenarians under study. However, present results do not exclude that differential expression of MMP-9 playing an opposite role in AMI and longevity because other kinds of regulation might be more relevant than those linked to the SNP under study.