[Genetic risk factors for development of myocardial infarction in young men living in North-West region of Russia].

With the aim to detect genetic factors of risk of development of early myocardial infarction (MI) we studied 29 allele variants of 19 genes in 206 men who had survived MI in the age before 45 years and in 195 men of similar age without cardiovascular diseases. All subjects were inhabitants of North-West region of Russia. The following factors were associated with history of myocardial infarction: genotype RR191 of paraoxonase-1 (PON1) gene (RR 2.8 [95% CI: 1.24 - 6.30]), P1A2 allele of glycoprotein (GP) IIIa subunit of platelet fibrinogen receptor GPIIb/IIIa (RR 1.8 [95% CI: 1.11 - 2.93]), and Met145 allele of GPIbalpha platelet von Willebrand factor receptor gene. Genotype CC ( - 108) PON1 was associated with lowered risk of MI development (RR 0.6 [95% CI: 0.40 - 0.91]). During 7 years of follow-up 30 men from MI group died of recurrent acute coronary syndromes. In the group of those who died we noted increased prevalence of P1A2 GPIIIa allele compared with those who survived (p < 0.03). The results allow to suggest that contribute to development of MI in young men factors associated with elevation of functional state of platelets and levels of oxidized lipids in blood plasma.

[Novel mutation of the GPIIIa gene in the Russian population, Leu40Arg, linked to the Leu33Pro].

Glycoprotein IIb/IIIa complex, a platelet surface fibrinogen receptor, plays a key role in producing primary hemostasis. At present, only a single mutation in the GPIIla gene, Leu33Pro, and a single mutation in the GPIIb gene, lle843Ser, has been described. The mutations are known to enhance signaling functions of the receptor and are associated with the development of arterial thromboses. In the present study, we describe a novel GPIIIa mutation, which is T to G nucleotide substitution in position 1585, resulting in the replacement of Leu for Arg in position 40 of the amino acid sequence of the protein.

[Allele Frequency Analysis of Four Single Nucleotide Polymorphisms Locating in Promoter and 5'-Untranslated Regions of ABCAI Gene in Young Men - Survivors From Myocardial Infarction]. / Analiz chastoty vyiavleniia chetyrekh strukturnykh polimorfizmov DNK v promotornoi i 5'-netransliruemykh oblastiakh gena ABCA1 u muzhchin, perenesshikh infarkt miokarda v molodom vozraste.

Analysis of allele distribution of four single nucleotide polymorphisms (C-17G, C69T, G-191C and 319insG) of promoter and 5'-untranslated regions of the ABCA1 gene was carried out in a sample of 171 men, who had survived myocardial infarction before 45 years, and in controls. Two-fold increase of T69 and C-191 allele frequencies were observed in Russian population in comparison to Dutch one. While comparing allele and genotype distributions of the polymorphisms in the samples under study no statistically significant differences were found, so as no influence of different alleles on lipid spectrum data was observed. Role of polymorphisms under study appears to be insignificant in formation of genetic susceptibility to myocardial infarction in young men.

[Changes in hemostasis system in patients with hereditary thrombophilia caused by mutation of blood coagulation factor V ( factor V Leiden)]. / Izmeneniia v sisteme gemostaza u bol'nykh s nasledstvennoi trombofiliei, obuslovlennoi mutatsiei faktora V svertyvaniia krovi (faktor V Leiden).

AIM: To study the incidence of mutation of Leyden's factor V in patients with venous thrombosis and the hemostatic system in carrier of this genetic defect. MATERIALS AND METHODS: A hundred and one patients aged 15-69 years who had venous thrombosis and 10 individuals with mutation of Leyden's factor V without manifestations in the history of thrombosis were examined. Factor V gene mutations and the thrombocyte and plasma links of hemostasis were determined by routine methods. RESULTS: The Leyden's factor V genotype Arg506-->Gln was detected in 17 of the 101 patients with venous thrombosis. Patients and asymptomatic individuals with this factor were found to have significant hypercoagulation, as evidenced by lower activated protein C-resistance index, higher factor VIII (von Willebrand's factor) activity, elevated von Willebrand's factor antigen levels, and enhanced intravascular platelet activation. In the presence of lupoid anticoagulant, hypercoagulation increased and protein C activity decreased. CONCLUSION: Detection of signs of hypercoagulation in patients with inherited thrombophilia at recovery in carriers of Leyden's factor V without clinical manifestations of thrombosis shows it necessary to make a particularly careful monitoring of the hemostatic system in these subjects. This is especially important for hypercoagulation-predisposing situations, such as pregnancy, surgical interventions, long-term immobilization, use of contraceptives, etc. when preventive measures may be used to prevent thrombotic events.

Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy in IDDM patients.

A missense mutation in the methylenetetrahydrofolate reductase gene (MTHFR), C677T, results in a thermolabile variant with reduced activity. Elevated levels of homocysteine have been recognized as a risk factor for vascular disease. Insulin-dependent diabetes mellitus (IDDM) is characterized by a higher prevalence of vascular complications. We analyzed the frequency of C677T MTHFR in IDDM and control groups. The genotype distribution did not differ between control subjects (n = 297) and IDDM patients (n = 392) (chi(2) = 5.413, df = 2, P > 0.05). The MTHFR T677T genotype was found significantly more frequently in IDDM patients with diabetic nephropathy (0.216) compared with the IDDM patients without nephropathy (0.056); the odds ratio was 2.635 (95% CI 1.768-3.927). Thus, we suggest that the T677T genotype of the MTHFR gene is an independent risk factor for diabetic nephropathy in IDDM.