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The polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene were tested for association with the frequency of unfavorable outcomes in patients with a history of acute ischemic heart disease. The study involved 1145 patients hospitalized in cardiology clinics of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don because of acute ischemic heart disease. The patients were followed up for up to 62.5 months. None of the markers displayed a significant association with the time to an endpoint. The patients were then grouped by sex. In females, the frequency of unfavorable outcomes (fatal or nonfatal myocardial infarction and fatal or nonfatal stroke) was higher in carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and carriers of genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene, but the difference was not statistically significant. Such an increase in frequency was not observed in males. To study the combined effect of the polymorphic markers of the THBD and F7 genes, the course of ischemic heart disease was compared for two female subgroups. One included carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene; the other subgroup included carriers of genotype Ala/Ala of the Ala455Val polymorphic marker of the THBD gene and allele Gln of the Arg353Gln polymorphic marker of the F7 gene. The frequency of unfavorable outcomes in the first subgroup was higher than in the second one. The time to an endpoin was 40.5 months (95% confidence interval (CI) 33.5–47.6) in the first subgroup and 51.6 months (95% CI 45.0–58.1) in the second subgroup (χ2 = 4.15, P = 0.042). The results made it possible to assume that the F7 and THBD genes play an important role in genetic predisposition to unfavorable outcomes in patients with a history of acute ischemic heart disease.

Association between the rates of poor outcomes in the patient cohort with acute coronary syndrome and polymorphisms G(−174)C in the IL6 gene and G(−1082)A in the IL10 gene were determined. In total, 1145 patients hospitalized for coronary artery disease to cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don were examined. The mean observation period was 9.10 ± 5.03 months (maximal, 18 months). Analysis of the survival of the patients with acute coronary syndrome that carried allele A has demonstrated that the presence of IL10 gene polymorphism G(−1082)A is associated with more frequent poor outcomes as compared with GG genotype. The survival time to endpoint for the carriers of GA and AA genotypes was 11.68 ± 0.67 months versus 12.69 ± 0.65 months for the carriers of GG genotype in IL10 gene (χ2 = 4.13, p = 0.042). As for the IL6 gene polymorphism G(−174)C, survival rate analysis did not detect any significant association with the risk for poor outcome. However, joint analysis of these polymorphisms in both genes has demonstrated that characteristic of the patients with acute coronary syndrome that carry GG genotype of IL6 gene and GA and AA genotypes of IL10 is a higher rate of poor outcomes (time to endpoint, 11.01 ± 1.24 months) as compared with the carriers of IL6 gene CC and CG genotypes and IL10 gene GG genotype (time to endpoint, 13.28 ± 0.83 months (ξ2 = 10.23, p = 0.017). These data suggest that the genes IL6 and IL10, whose products are involved in the control of inflammatory response, play an important role by increasing the probability of poor outcomes in the patients with acute coronary syndrome.

The applicability of real-time PCR amplification of the chromosome Y marker DYS14 for sex determination was studied. With this aim, real-time PCR of DYS14 (located within the TSPY1-encoding gene) was performed in plasma DNA specimens obtained from 30 men and 30 women. The PCR results showed that 30 specimens were of male and the other 30 were of female origin. All the results were confirmed by the tests for the SRY marker conventionally used in forensic examination. The detection limit for the DYS14-containing DNA region was established in dilution experiments and was equal to 6.7 pg of DNA (two copies of the genome), which corresponds to 6.7 ng of DNA (2000 copies of the genome) in 1 ml of blood. This level of sensitivity allows sex determination in specimens with small amounts of genetic material. The method can be used for noninvasive prenatal diagnostics of sex-linked congenital diseases and in forensic medical examination.

The possibilities of real-time PCR amplification of DYS14 marker located on Y chromosome for sex determination were studied. Samples of plasma of 30 men and 30 women were investigated for this aim. Real-time PCR amplification of DYS14 marker (located inside gene coding TSPY1 protein) was used for sex determination. According to the obtained results, 30 samples belonged to men and 30--to women. In all our experiments the results were confirmed by use of marker SRY, widely used in forensic examination. Detection limit of DNA region containing DYS14 in reaction mixture was established after experiment with dilution of male DNA and is equal to 6.7 pg of DNA (two copies of genome), which corresponds to 6.7 ng of DNA (2000 copies of genome) in 1 ml of blood. Sex determination with small amounts of genetic material in investigated sample becomes possible with such characteristics. Method can be used for noninvasive prenatal diagnostics for the timely detection of congenital diseases associated with sex and in forensic medical examination.