2658-6533Research Results in Biomedicine2658-653310.18413/2313-8955-2018-4-3-0-21503GeneticsMOLECULAR-GENETIC ANALYSIS OF ASSOCIATIONS OF POLYMORPHOUS GENES COMBINATIONS OF THE XENOBIOTICS BIOTRANSFORMATION WITH THE ISOLATED VENTRICULAR SEPTAL DEFECT DEVELOPMENT IN THE KRASNODAR TERRITORYMOLECULAR-GENETIC ANALYSIS OF ASSOCIATIONS OF POLYMORPHOUS GENES COMBINATIONS OF THE XENOBIOTICS BIOTRANSFORMATION WITH THE ISOLATED VENTRICULAR SEPTAL DEFECT DEVELOPMENT IN THE KRASNODAR TERRITORYLazarevKonstantin Yu.LazarevKonstantin Yu.lazarev_ku@mail.ruBraikoOlga P.BraikoOlga P.20184300

Background: The study of the involvement of polymorphisms of candidate genes of the biotransformation system of xenobiotics in the formation of congenital malformations in children is one of the urgent problems of modern medicine. The aim of the study: To estimate the polymorphous genes associations of the xenobiotic biotransformation system with ventricular septal defect predilection in children in Krasnodar region. Materials and methods: Children with verified VSD (100 participants), mean age 3.11+0.85, were tested in the research,. The parents (without congenital minimum effective temperature) of children with VSD were tested as a population group. The participants were the innates of the Krasnodar Territory and belonged to the Slavic nationality. The DNA and polymorphous genes amplification were made in the real time mode; the derived genotypes were analysed by the alleles’ discrimination method. The x2 criterion, for concordance estimation genotypes distribution of expected meanings by Hardy- Weinberg equilibrium and for the comparison of frequency genotypes and alleles distribution (among healthy and diseased patients), were used. Results: The statistical validity (having high risk of VSD formation) of 5 genotypes combinations was revealed: CYP1B 1432AA x NAT2 590GG, CYP1B1 432GG x CYP03A4 664TT, CYP3A4 664TT x CYP3A5 6986AA – male gender, CYP1B1 432AG x NAT2 590AA, CYP2C9 1075AC x CYP3A4 664TC – female gender, with indices (р<0.05, OR=3.29, 95% CI=1.11-9.74), (р<0.05, OR=14.23, 95% CI=1.72-117.86), (р<0.05, OR=4.75, 95% CI=0.98-23.10), (р<0.05, OR=2.66, 95% CI=0.95-7.41), (р<0.05, OR=7.07, 95% CI=0.77-64.83), including 3 combinations of protective character NAT2 590GA х ABCB1 3435CT (р<0.05, OR=0.37, 95% CI=0.15-0.94), CYP1B1 432АА х CYP2C9 1075AA (р<0.05, OR=0.40, 95% CI=0.17-1.00) – male gender, CYP2C9 1075AC х CYP3A56986AA (р<0.05, OR=0.36, 95% CI=0.13-1.03) – female gender. Conclusion: Eight pairs of combinations of genotypes of xenobiotic biotransformation enzymes associated with the risk of developing an isolated defect of the interventricular septum were established.

Background: The study of the involvement of polymorphisms of candidate genes of the biotransformation system of xenobiotics in the formation of congenital malformations in children is one of the urgent problems of modern medicine. The aim of the study: To estimate the polymorphous genes associations of the xenobiotic biotransformation system with ventricular septal defect predilection in children in Krasnodar region. Materials and methods: Children with verified VSD (100 participants), mean age 3.11+0.85, were tested in the research,. The parents (without congenital minimum effective temperature) of children with VSD were tested as a population group. The participants were the innates of the Krasnodar Territory and belonged to the Slavic nationality. The DNA and polymorphous genes amplification were made in the real time mode; the derived genotypes were analysed by the alleles’ discrimination method. The x2 criterion, for concordance estimation genotypes distribution of expected meanings by Hardy- Weinberg equilibrium and for the comparison of frequency genotypes and alleles distribution (among healthy and diseased patients), were used. Results: The statistical validity (having high risk of VSD formation) of 5 genotypes combinations was revealed: CYP1B 1432AA x NAT2 590GG, CYP1B1 432GG x CYP03A4 664TT, CYP3A4 664TT x CYP3A5 6986AA – male gender, CYP1B1 432AG x NAT2 590AA, CYP2C9 1075AC x CYP3A4 664TC – female gender, with indices (р<0.05, OR=3.29, 95% CI=1.11-9.74), (р<0.05, OR=14.23, 95% CI=1.72-117.86), (р<0.05, OR=4.75, 95% CI=0.98-23.10), (р<0.05, OR=2.66, 95% CI=0.95-7.41), (р<0.05, OR=7.07, 95% CI=0.77-64.83), including 3 combinations of protective character NAT2 590GA х ABCB1 3435CT (р<0.05, OR=0.37, 95% CI=0.15-0.94), CYP1B1 432АА х CYP2C9 1075AA (р<0.05, OR=0.40, 95% CI=0.17-1.00) – male gender, CYP2C9 1075AC х CYP3A56986AA (р<0.05, OR=0.36, 95% CI=0.13-1.03) – female gender. Conclusion: Eight pairs of combinations of genotypes of xenobiotic biotransformation enzymes associated with the risk of developing an isolated defect of the interventricular septum were established.

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