SupplementaryTable.The functional significanceof genetic variants selected for analysis of association with myocardial infarction (MI)

Gene symbol / Coding protein / Implication of the protein in atherosclerosis or atherosclerosis-related diseases [Reference] / Geneticvariants,rs ID / Known (putative) effects of SNP or ORF shift on the level/activity of the product [Reference]
CRP / C-reactive protein / Increased levels of C-reactive proteinare associated with risk of MI and stroke [1] / 1444C>T
rs1130864 / Allele T is associated with increased plasma levels of C-reactive protein [2]
IL10 / Interleukin 10 / Interleukin 10 is involved in the anti-atherogenic effects [3] / −1082G>A
rs1800896 / Allele G determines the high-production of interleukin 10[3]
MTHFR / 5,10-Methylenetetrahydro-folate reductase / Hyperhomocysteinemia may affect endothelial function and integrity, so it is a risk factor for atherosclerosisand cardiovascular diseases [4] / 677C>T
rs1801133 / Individuals homozygous for T allele have significantly elevated plasma homocysteine levels [5]
CTLA4 / Cytotoxic T-lymphocyte antigen 4 (CTLA-4) / CTLA-4 regulates proatherogenic immune responses [6] / 49A>G
rs231775 / CTLA-4 cell-surface expression is significantly increased in individuals carrying genotype A/A [7]
CCR5 / C-C chemokine receptor type 5 (CCR5) / CCR5 participates in recruitment of monocytes in developing atherosclerotic plaques [8] / Frameshift variant
rs333 / ORF shift. Carriage of the homozygous genotype del32/del32 results in a failure to express the receptor on the cell surface, while the heterozygous carriers express less receptor than wild-type homozygotes [9]
FGA / Fibrinogen alpha chain / High plasma level of fibrinogen is a risk factor for cardiovascular diseases [10] / 4266A>G
rs6050 / Allele A correlates with stiffer clots [11]
FGB / Fibrinogen beta chain / −249C>T
rs1800788 / Allele T is associated with greater plasma fibrinogen levels [12]
PDE4D / Phosphodiesterase 4D / Phosphodiesterase 4D regulates cAMP-dependent signaling pathway in many cells types. Reducing of cAMP level increases the proliferation and migration of smooth muscle cells and may contribute to the development of atherosclerosis [13] / 41G>A
rs152312 / Unknown
IL4 / Interleukin 4 / Interleukin4 participates in immune cell chemotaxis, cell adhesion and has pleiotropic effects in atherosclerosis [14,15] / −590C>T
rs2243250 / Allele T is associated with higher promoter activity and increased production of interleukin4as compared to C allele [16]
TNF / Tumor necrosis factor (TNF), formerly known as TNF alpha / TNF together with other cytokines is involved in inflammation underlying atherosclerosis [17] / −308G>A
rs1800629 / Allele A determines the enhanced production of TNF [18]
LTA / Lymphotoxin alpha / Lymphotoxin alpha is involved in atherogenesis and increases the growth of atherosclerotic plaques[19] / 252A>G
rs909253 / Allele G correlates with elevated circulating lymphotoxinalpha level [20]
IL6 / Interleukin 6 / The upregulationof interleukin 6 is associated with carotidatherosclerosisand plaque instability [21] / −174G>C
rs1800795 / Allele C is associated with significantly lower levels of plasma interleukin 6[22]
PAI1 / Plasminogen activator inhibitor-1 (PAI-1) / PAI-1 may play a key role in the progression of cardiovascular aging by promoting thrombosis and vascular atherosclerosis [23] / −675 4G>5G
rs1799889 / Allele 4G is associated with greater circulating levels of PAI-1 [24]
ENOS / Endothelial nitric oxide synthase (eNOS) / The eNOS dysfunction can cause several cardiovascular diseases such as atherosclerosis, hypertension and thrombosis [25] / −786T>C
rs2070744 / Allele C is associated with a reduction of eNOS mRNA expression and a corresponding reduction of eNOS protein [26]
PLAT / Tissue plasminogen activator (tPA) / tPA is involved in fibrinolysis. Abnormalities in the fibrinolytic system are implicated in the pathogenesis of atherosclerosis-related diseases such as MI and stroke [27] / −7351C>T
rs2020918 / T allele confers a reduced transcriptional activity in vitro and reduced tPA release in vivo [28]
LPL / Lipoprotein lipase(LPL) / LPL is a central enzyme in overall lipid transport and metabolism and participates in the pathogenesis of atherosclerosis [29] / 1595C>G
rs328 / G allele (X447 stop variant)isassociatedwithincreasedLPLactivity, lowerplasmatriacylglycerols, higherhigh-densitylipoproteinandreducedriskofcoronary heart disease [30]
PTGS1 / Prostaglandin-endoperoxide synthase 1, also known as сyclooxygenase-1 (COX-1) / COX-1is a target for non-steroidal anti-inflammatory drugs, which are frequently used in the treatment of cardiovascular diseases [31] / 50C>T
rs3842787 / 50C>T change in PTGS1 gene results in significantly increase COX-1 sensitivity to inhibition by indomethacin in vitro [32] and by aspirin ex vivo [33]
IFNG / Interferon gamma / The interferongamma, a pleiotropic cytokine, is one of the key regulators of atherosclerosis with both pro- and anti-atherogenic actions [34] / 874A>T
rs2430561 / Allele T correlates with high interferongamma expression level [35]
TGFB1 / Transforming growth factor beta 1 (TGF-β1) / TGF-β1 is a pleiotropic growth factor. It is involved in the induction of intimal thickening during atherogenesis [36] / 869T>C
rs1982073 / Allele C correlates with increased TGF-β1 plasma levels [37]
APOE / Apolipoprotein E / Apolipoprotein E is a lipid transport protein and major ligand for low-density lipoprotein (LDL) receptors. It plays a key role in cholesterol metabolism and cardiovascular diseases [38] / epsilon polymorphism
(rs7412, rs429358) / Individuals carrying the APOE epsilon 4 allele have increased total cholesterol, LDL-cholesterol and decreased apolipoprotein E plasma level[39]

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