CYP2C19*2 gene variant (G681A, rs4244285) as a prognostic marker for the clinical course of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the most common type of paraproteinemic hemoblastosis, which is characterized by an aggressive course, high mortality and a large number of complications. The G681A variant (*2, rs4244285) of the CYP2C19 gene leads to the formation of an inactive enzyme and, as a consequence, may affect the development and course of MM. The aim of this research was to analyze the effect of the G681A variant of the CYP2C19 gene on the risk of the development of MM and its course. MATERIALS AND METHODS: The study enrolled 158 patients with MM, who underwent standard clinical and laboratory studies: cytological, general clinical, biochemical, as well as molecular cytogenetic and molecular genetic. Cytogenetic analysis of chromosome abnormalities was performed using interphase fluorescence in situ hybridization. Genotyping by the G681A variant of the CYP2C19 gene was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association was found between the G681A variant of the CYP2C19 gene and the risk of developing MM. The association between the presence of the G allele and GG genotypes with significant changes in clinical and biochemical parameters (plasma cell count, α2-globulin, calcium content) in MM patients has been established. In the presence of the G allele of the CYP2C19 gene, the development of chromosomal rearrangements del(13q14.2) or del(13q34) with significantly increased levels of albumin occurs more frequently. CONCLUSIONS: The G681A variant of the CYP2C19 gene does not affect the risk of developing MM, but it is associated with significant changes in the clinical and biochemical parameters that determine the severity of the disease and its prognosis. Further research is important to develop new target strategies and maintenance therapy for carriers of different variants of the CYP2C19 gene (G681A).

ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

BACKGROUND: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors. AIM: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants. MATERIALS AND METHODS: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy). RESULTS: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ2 = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ2 = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy. CONCLUSIONS: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

A variant of TP53 gene (rs 1625895, 13494g>A) is associated with neoplasm localization in patients with uterine leiomyoma.

BACKGROUND: Uterine leiomyoma (UL) is the most common benign neoplasm of the uterus. It is still unknown surely what exactly initiates transformation of the uterine myometrial cells into UL. AIM: To study the effect of the TP53 gene variants on the risk of development and clinical features of UL. MATERIALS AND METHODS: Case-control study was performed using molecular genetic analyses of variants rs1042522 (119 G>C) and rs1625895 (13494G>A) of TP53 gene in patients with UL and comparison group of healthy women. RESULTS: Investigated TP53 gene variants were not associated with the risk of UL development. The patients with the 13494GG genotype (rs1625895) had significantly more often subserous UL (р < 0.05). In patients with heterozygous variant of TP53 - 13494GA genotype (rs1625895) intramural UL was observed (р < 0.05). CONCLUSIONS: The rs1625895 (13494G>A) variant of TP53 gene was associated with UL localization. The identified dependence of the UL localization on the TP53 gene variant could be useful for personalized approach to treatment.

Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue.

BACKGROUND: Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. AIM: To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. MATERIALS AND METHODS: Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. RESULTS: Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region - in 50% of cases, and hypermethylation of the promoter region of both genes - in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. CONCLUSIONS: The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.

POSITIVE EFFECT OF BETAINE-ARGININE SUPPLEMENT ON IMPROVED HYPERHOMOCYSTEINEMIA TREATMENT IN MARRIED COUPLES WITH REPRODUCTIVE DISORDERS.

Treatment of hereditary hyperhomocysteinemia and the achievement of optimal folate status is necessary for persons of reproductive age in order to increase live birth rate. Patients are usually advised to take folic acid, a key nutrient in homocysteine remethylation. The results of study showed risk factors for hyperhomocysteinemia development in investigated married couples: male gender, MTHFR, MTR1 genes variants, lower vitamin B12 blood serum and no additional intake of vitamin B12. Since MTHFR, MTR1 genes variants affect to decrease the efficiency of homocysteine metabolic transformations, to contribute also to endothelial dysfunction in one of patients group we used betargine combined with folic acids and vitamin B12 administration. Patients group with combined administration including betargine within 2 weeks, in comparison with the group without its supplement, had significantly decreased level of homocysteine in plasma, less than 12 µmol/l (81.03% and 50% of cases, respectively). Folic acid and vitamin B12 mean values in blood serum was significantly increased in patients after two week vitamins administration including betargin. Further research is needed to establish the duration of betaine-arginine intake until the target homocysteine level will be reached, as well as to estimate the durability of clinical effect achieved after consumption.