الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Introduction: Ischemic heart disease (IHD) is the leading causes of mortality worldwide. IHD is a multifactorial disease with a complex pathogenesis, however, the genetic role has not been explained yet. In premature IHD, the role of genetic risk factors should be more important. Although the association between inherited thrombophilia and venous thrombotic diseases are well-established, controversial data are present on its association with IHD.
Subjects & Methods: The present study consisted of 72 subjects; 52 patients who suffered from premature IHD < 40 years (46 males and 6 females), and 20 apparently healthy individuals (17 males and 3 females), who served as the control group. The patients were classified according to their clinical data and investigations into the following two groups: AMI group: 31 patients; and UA group: 21 patients. All subjects were subjected to thorough history taking, clinical and ECG examination and laboratory investigations (cardiac markers, lipogram, lupus anticoagulants screening, antiphospholipids IgG/lgM and anticardiolipin IgG/lgM antibodies). Samples were taken for DNA extraction and typing with CVD StripAssay for the identification of mutations associated with CVD based on polymerase chain reaction (PCR) and reverse-hybridization molecular technique. The assay covers 12 polymorphisms: FV G1691A (Leiden), FV H1299R (R2), Prothrombin G20210A, Factor XIII V34L, β-Fibrinogen -455 G-A, PAI-1 4G/5G, GPIIIa L33P (HPA-1), MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q, and Apo E2/E3/E4 polymorphisms. Statistical analysis of the results was carried out using Statistical Package for Social Scientists (SPSS) program, version 15.0.
Results: We explored increased risks for premature AMI with FV Leiden (GA: OR. 6.48, 95%CI. 1.56-26.84, P=0.008; A allele: OR.5.05, 95%CI. 1.38-18.48; P=0.01), Prothrombin G20210A heterozygosity (GA: OR. 4.67, 95%CI, 1.13-19.24; P=0.035), and ACE (I/D) polymorphisms (D allele: OR. 2.46; 95%CI, 1.09-5.56; P= 0.047), compared with the control group. In UA patients group, the heterozygous (GA) genotype, and the (A) allele of Fibrinogen β-455 G->A polymorphism were associated with increased risk for UA, compared with the control group (GA: OR. 9.0; 95%CI: 1.98-40.93; P=0.004; A allele: OR. 3.0; 95%CI: 1.12-8.05; P=0.034). In addition, there were significant decreases in the frequencies of heterozygous (GT), and T allele of FXIII Val34Leu in UA patients group, compared with the control group (P=0.042, 0.011), assuming a protective role of FXIII 34Leu allele against UA development. The prevalence of other studied polymorphisms did not differ between IHD patients and control subjects. There was a significant positive association between FVL and family history of IHD in AMI patients (P=0.029). In addition, an age-related change in the prevalence of the PlA2 genotype showing highest prevalence of Pl A2 in patients <35 years of age surviving a first AMI, so that age-at-onset of AMI was significantly affected by PlA2 (<35 years vs. 35-40; OR. 14.63, 95%CI. 1.55-138.19, P=0.006). Apo E3/E4 genotype was associated with both high total Cholesterol (TC) and high TC/HDL ratio (P<0.0001 for both) in UA group, while in AMI patients, Apo E3/E4 genotype was associated with high TC/HDL ratio, with OR of 27.00 (95%CI, 3.09-235.73; P=0.002), and high triglycerides levels (P< 0.001).
Conclusions: FV Leiden, Prothrombin G20210A heterozygosity, and ACE (I/D) polymorphisms are risk factors for premature AMI; β-fibrinogen 455-GA polymorphism is risk factor for premature UA patients; and FXIII Val34Leu has a protective role against early-onset UA patients.
Recommendations :
• It is possible to screen and use specific thromboprophylaxis to prevent recurrent thrombotic diseases in high risk young IHD patients (< 40 years). Genetic counseling to the family permits to extend the analysis (and prophylaxis in the case) to other consanguineous that bear the same prothrombotic predisposition. Taken together, this may eventually lead to the promised goals of new therapeutics and personalised medicine for premature IHD based on single nucleotide polymorphism.
• Further researches for confirmation of our findings by a large-scale evaluation should be considered or by prospective studies on a large series of young healthy individuals followed up until they reach the end points of IHD.