Abstract
BackgroundAcute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs). However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated.ResultsThis study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4%) and patients with sporadic AMI (31.8%) than in the CTR (17.3%) and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224). During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events.ConclusionOur data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity for cardiovascular diseases. This inflammatory genetic profile, along with classical cardiovascular risk factors, may be used for better defining individual risk of AMI in unaffected subjects.
Highlights
Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved
The percentage of VEGF C carriers was significantly higher in the AMI group than in the CTR (95.3% vs 84.5%, p = 0.0001; odds ratios (OR) = 3.735), whereas the percentage of A carriers was significantly lower in the Offs (37.7%, p = 0.0001) and the AMI group (35%, p = 0.0001; OR = 0.373) than the CTR (59.1%)
Recent genome-wide association (GWA) studies have contributed substantially to the discovery of new single nucleotide polymorphisms (SNPs) associated with coronary heart disease (CHD) and AMI [23], but their clinical relevance is still unclear because a single gene variant can make a limited contribution to the total genetic load of AMI, and both common and rare gene polymorphisms may differentially affect susceptibility to the disease
Summary
Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. A family history of cardiovascular diseases (CVD) and AMI is frequently encountered in clinical practice, and a premature heart attack in parents is associated with a high risk of the disease in their offspring (Offs) [13]. This initial observation has been confirmed and extended by other studies showing that parental CVD is a risk factor for CVD in middle-aged Offs [14]. The Framingham Heart Study has shown that parental stroke before the age of 65 years is associated with a 3-fold increase in the risk of stroke in their Offs, and that parental history can be used as clinical risk marker of an individual’s propensity to stroke [21]
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