Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis.

BACKGROUND: Raised SERPINE1 plasma levels are related to a 1-bp guanine deletion/insertion (4G5G) polymorphism in the promoter of the SERPINE1 (plasminogen activator inhibitor 1 - PAI1) gene. Evidence suggested that the plasma levels of SERPINE1 modulate the risk of coronary artery disease; furthermore, that the 4G5G polymorphism affects the expression of the SERPINE1 gene. AIM: To analyse association of SERPINE1 polymorphism with occlusive artery disease (OAD) and deep venous thrombosis (DVT) in Macedonians in order to investigate its role as a part of candidate genes in different vascular diseases in Macedonians. METHODS: Investigated groups consisted of 82 healthy patients, 75 with OAD, and 66 with DVT. Blood samples were collected after written informed consent was obtained, and DNA was isolated from peripheral blood leukocytes. Identification of SERPINE1 polymorphism was done with CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). The population genetics analysis package, PyPop, was used for analysis of the SERPINE1 data. Pearson's P-values, crude odds ratio and Wald's 95% CI were calculated with Bonferroni corrected p value. RESULTS: The frequency of 4G allele for SERPINE1 was 0.538 for DVT, 0.555 for healthy participants, and 0.607 for OAD. The frequency of 5G allele for SERPINE1 was the smallest in patients with OAD (0.393) and was higher in healthy participants (0.445), and patients with DVT (0.462). Test of neutrality (Fnd) showed negative value, but was significantly different from 0 for SERPINE1 in healthy participants (p of F = 0.041) and in patients with DVT (p of F = 0.030). SERPINE1 genotypes in healthy participants and patients with OAD were not in Hardy Weinberg proportions (p = 0.019 and 0.001, respectively). No association between SERPINE1 polymorphisms and OAD or DVT was found. CONCLUSION: There is no significant relationship between SERPINE1 polymorphisms and occlusive artery disease or deep venous thrombosis in Macedonian population.

Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis.

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT.

Association of methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genetic polymorphisms with occlusive artery disease and deep venous thrombosis in Macedonians.

AIM: To analyze the association of methylenetetrahydrofolate reductase polymorphisms (MTHFR-677 and MTHFR-1298) with occlusive artery disease and deep venous thrombosis in Macedonians. METHODS: We examined 83 healthy respondents, 76 patients with occlusive artery disease, and 67 patients with deep venous thrombosis. Blood samples were collected and DNA was isolated from peripheral blood leukocytes. Identification of MTHFR mutations was done with CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Vienna, Austria) and the population genetics analysis package, PyPop, was used for the analysis. Pearson P values, crude odds ratio, and Wald's 95% confidence intervals were calculated. RESULTS: The frequency of C alleles of MTHFR-677 was 0.575 in patients with deep venous thrombosis, 0.612 in patients with occlusive artery disease, and 0.645 in healthy participants. The frequency of T allele of MTHFR-677 was lower in healthy participants (0.355) than in patients with occlusive artery disease (0.388) and deep venous thrombosis (0.425). The frequency of A allele for MTHFR-1298 was 0.729 in healthy participants, 0.770 in patients with occlusive artery disease, and 0.746 in patients with deep venous thrombosis. The frequency of C allele of MTHFR-1298 was 0.271 in healthy participants, 0.230 in patients with occlusive artery disease, and 0.425 in patients with deep venous thrombosis. No association of MTHFR-677 and MTHFR-1289 polymorphisms with occlusive artery disease and deep venous thrombosis was found, except for the protective effect of MTHFR/CA:CC diplotype for occlusive artery disease. CONCLUSION: We could not confirm a significant association of MTHFR-677 and MTHFR-1289 polymorphisms with occlusive artery disease or deep venous thrombosis in Macedonians, except for the protective effect of MTHFR/CA:CC diplotype against occlusive artery disease.