Acute Myocardial Infarction and Proinflammatory Gene Variants

Abstract

We identified four genetic risk sets for acute myocardial infarction (AMI) from information on functional gene variants that favor inflammation or modulate cholesterol metabolism: IL6 -174 G/C, TNF -308 G/A, IL10 -1082 G/A, SERPINA3 -51 G/T, IFNG +874 T/A, HMGCR -911 C/A, and APOE epsilon2/3/4; 316 patients and 461 healthy subjects, all Italian. Putative risk alleles are shown underlined. The sets were identified using grade-of-membership analysis. Membership scores in the sets are automatically generated for individuals. The 'low intrinsic risk' set had alleles that downregulate inflammation and cholesterol synthesis (IL6, TNF, ILl0, HMGCR). 'AMI across a broad age range' carried multiple proinflammatory alleles (IL6, TNF, IL10, SERPINA3): All 72 persons like this set were affected yet had relatively low plasma cholesterol levels. 'A subset of AMI in middle age' had numerous proinflammatory alleles (IL6, TNF, SERPINA3, IFNG, HMGCR). 'AMI after age 80' had a reduced risk set (IL6, IL10, IFNG). A total of 95% of cases had >/=50% membership in the high intrinsic risk sets. We conclude that proinflammatory gene variants taken together strongly determine an individual's risk for myocardial infarction. This information may better define the pathogenesis of myocardial infarction and identify individuals who might benefit from early interventions.

Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients

“…Results reported in Table 1 confirm reports from previous researches [13,14] on the role of TNF À308A allele in AMI and suggest that this gene variant might be an AMI risk factor for young men but do not allow to confirm the association between FII 20210A allele and AMI. To date, actually, studies attempting to answer this question have yielded conflicting results.…”

“…In previous studies we have demonstrated that proinflammatory gene variants determine an increased individual's risk for myocardial infarction [14]. Table 1 shows the analysis of genotypic frequencies of the single nucleotide polymorphisms of TNF (À308G/A) an of the prothrombin (factor II, FII 20210G/A) among the 60 male patients and 130 healthy controls.…”

“…The single nucleotide polymorphisms (SNPs) present in the genes CD14 (À159 C/T), TNFa (À308 G/A), IL-1a (À889 C/T), IL-6 (À174 G/C), PSMA6 (À8 C/ G), and PDE4D (SNP83 T/C, respectively), were found to be associated with increased risk of cardiovascular diseases in different populations [7][8][9][10][11][12]. In addition previous studies have shown that polymorphisms of genes encoding key factors for the control and activation of inflammatory response may play a role in genetic susceptibility to AMI in young men [13,14].…”

Genetics of Myocardial Infarction

“…Analyzing polymorphisms in seven candidate genes related to cholesterol metabolism and proinflammatory status (including IL-6, TNF, IL-20, HMGcoR, and apoE) [11], Licastro identified individuals with low and high risk using a statistical model. Proinflammatory gene variants taken together determine an individual risk for MI, especially in young age.…”

“…A dominant portion of candidate genes studied is related to lipoprotein metabolism (15%) and inflammation (16%), followed by genes determining arterial wall behavior after atherogenic stimuli (12%) and then to blood pressure regulation, monocyte activity, oxidation, and coagulation (6-8%). whereas in the late nineties attention was focused on lipoprotein metabolism [1,15] and blood pressure regulation, more attention has been paid to inflammation and atherothrombosis-regulating genes [11,16].…”