OP10. ASSOCIATION BETWEEN UTERINE LEIOMYOMA AND ESTROGEN METABOLISM AND ESTROGEN RECEPTOR GENES POLYMORPHISMS IN RUSSIAN POPULATION (BASHKORTOSTAN) EGOROVA O.V.1, Bermisheva M.A.1, Khusnutdinova E.K.1, Glebova N.N.2, Dodonov A.N.2
1 Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian
Academy of Sciences, Ufa, Russia; 2 Bashkortostan State Medical University, Ufa,
Russia
email: olga_423@web.de
*Corresponding Author: page: 39
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Abstract
Leiomyoma, the most common benign uterine neoplasm, occurs in around one-forth of women during their lifetimes. Leiomyoma is caused by a complex interaction between multiple genes, hormone, growth factor, cytokines, and the environment. Estrogen production and metabolism play critical roles in the development and pathogenesis of uterine leiomyoma. Cytochrome P450 1A1 (CYP1A1), catechol-O-methyltransferase (COMT) and glutation-s-transferase (GSTM1) are key enzymes in the estrogen metabolism pathway that result in the hydroxylation, methylation and conjugation of estradiol, respectively. Estrogen receptors (ESR1) are important mediators of hormonal bioeffects. We evaluated the association between the GSTM1 null-allele, CYP1A1 Ile462Val, the COMT Val158Met and the ESR1 PvuI and XbaII polymorphisms and uterine leiomyoma risk in a case-control study: 170 women with and 75 without uterine leiomyoma living in the Bashkortostan (South Ural region of Russia). A polymorphic sites of the genes was amplified by polymerase chain reaction (PCR), restricted (with the exception of GSTM1) and electrophored on agarose gel. Genotypes and allelic frequencies for studied polymorphisms in both groups were compared. There was no significant difference between the two groups regarding the distribution of the GSTM1, CYP1A1 and ESR1 genes polymorphisms frequencies (p>0.05). The frequency of the low-activity COMT Met/Met genotype was significantly higher in patients than in the healthy control group (62 % and 12%, respectively: x2=14.15, p=0.008). This genotype was associated with increased risk of uterine leiomyoma in Bashkortostan population (OR=5.16, 95% CI 2.03-13.65).
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