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Journal Technologies of Living Systems №4 for 2009 г.
Article in number:
ASSOCIATIVE INVESTIGATION OF DNA POLYMORPHISM RELATIVE TO THE RISK OF THE DISEASES OF FEMALE REPRODUCTIVE SPHERE
Keywords: DNA polymorphism leyomiomas fibrous mastopathy association study gene-gene interactions
Authors:
L.E. Salnikova, T.I. Ivanova, T.V. Kondrashova, L.I. Krikunova, N.I. Shentereva, I.A. Smirnova, I.A. Zharikova, N.Sh. Lapteva, A.G. Chumachenko, N.I. Ryabchenko, A.V. Rubanovich
Abstract:
The diseases of reproductive sphere of females (uterus mioma, fibroadenoma, mammary adenoma, fibrous-cystous mastopathy, etc.) are undoubtedly related to socially important diseases. Despite of the wide spreading and the presence of genetic and ecological components, the contribution of natural genetic variability into the predisposition to nononcological diseases of the reproductive system is practically unknown. The goal of this work was to study the conjugation of the polymorphism of genes of detoxication of xenobiotics and redox balance with the diseases of the reproductive sphere of females living in the regions of the Tula and Bryansk oblast radiation-polluted after the Chernovyl Nuclear Station accident. Among the polymorphous loci, the products of which can influence the resistance of living organisms to hazardous factors and the antioxidant potential of cell, are the genes of glutathione-S-transferases, catechol-O-methyltransferase inactivating catechol estrogens, and the gene of hemochromatose controlling the content of free iron. In the paper, the results of the associative analysis of DNA polymorphism in females living in the Central Russia and suffering from diseases of the female reproductive sphere, fibrous-cystous mastopathy (FCM) and miomas (379 patients and 117 of the control group), are presented. PCR genotyping was carried out for polymorphous loce related to the detoxication of xenobiotics, oxida-tive stress, and metabolism of estrogens (GSTM1, GSTT1, GSTP1, COMT, HFE187, and HFE845) as well as a gene responsible for the synthesis and methylation of DNA (MTHFR). The genotypic and allele frequencies by the individual loci in the groups under investigation were practically the same except of MTHFR locus in the group of females with both diseases (mioma and FCM): allele 677T corresponding to a lowered enzyme activity was observed significantly more frequently compared to the control group (OR=1.8, P=0.019). By analyzing the frequencies of combinations of the genotypes of different loci, the significant association of diseases with double homozygotes COMT H/H-GSTP1 A/A by alleles typical of the enhanced enzyme activity (OR=2.3-2.6, P=0.050) was found. The maximum conjugation with the risk of the development of the above pathology was noted for a minor allele combination TG of MTHFR-HFE187 loci for the additive model of inheritance (OR=11.4, P=0.014). In discussion part, the possible mechanisms of the revealed associations with regard for es-trogen-dependent character of diseases of the female reproductive sphere are considered.
Pages: 42-49
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