TaqI polymorphism of VDR gene in colorectal cancer and Crohn’s disease patients

УДК: 616.345+616.351)]-006.6-06:616.344-002-031.84:575.113](477.8)

To study the relation of TaqI polymorphism of VDR gene with age, sex and the disease phenotype in patientswith colorectal cancer (CRC) and Crohn’s disease (CD) from western regions of Ukraine. Fifty six patientswith CRC, 46 patients with CD and 65 control individuals were included in this research. Assessment of TaqI polymorphism was performed using PCR-RFLP method. The genotype-phenotype association for this polymorphism was analyzed. The frequency of tt genotype in patients with CRC is 0.107 and among the control group is 0.138, OR (95% CI 0.248-2.246). The ratio of genotypes TT:Tt:tt in patients with CRC and in control was 37.5%:51.8%:10.7% and 44.6%:41.6%:13.8%. In men with Tt genotype the average age of CRC onset was 57.6 ± 3.6 years, in women with TT genotypethe mean age of the disease onset was 54.5 ± 4.5 years. The frequency of tt genotype in the patients with CD is 0.217 and among the control group is 0.138, OR (95% CI 0.640–4.666). The Tt genotype was detected in a half of patients with CD and TT genotype was found more frequently in control.The ratio of genotypes in men and women with CD was 38.0%:38.0%:24.0% and 20.0%:60.0%:20.0%. Among patients with CD, who underwent surgery, 33.3% individuals were carriers of tt genotype. It was confirmed no statistically significant difference in the allele frequencies and genotype distributions of Taq1 mutation in patients with CRC and CD in comparison to control group. The ratio of men and women with Tt genotype by groups of B1-B3 forms of CD behaviour according to the Montreal classification is differs, in particular, women with Tt genotype are four times more likely to have the B1 form. A study of Taq1 mutation might contribute to the identification of the groups that are at the greatest risk of severe form of CD.

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Acute toxicity, anti-inflammatory and hypoazotemic activity study of anemone nemorosa extracts in rats

UDC 615.322:615.451.1

Actuality. The widespread use of herbal drugs with anti-inflammatory and nephroprotective properties stimulates the search for new active biological substances. Of particular interest are plants from the Ranunculaceae family, especially Anemone nemorosa, which contains a range of potentially bioactive components such as anemonin, protoanemonin, and others. Understanding the acute toxicity, anti-inflammatory, and hypoazotemic activity of Anemone nemorosa extracts opens possibilities for the development of new therapeutic agents based on this plant. Materials and methods. Ethanol extracts were obtained from the aerial parts of Anemone nemorosa harvested during the flowering period. The study included the examination of oral acute toxicity conducted on Wistar rats over 14 days, anti-inflammatory activity using the carrageenan-induced paw edema method in Wistar rats, and hypoazotemic activity on models of healthy and acute renal failure in Wistar rats. Results. The extracts showed no acute toxicity at the administered dose. It was established that the oral administration of the extracts is non-toxic up to a dose of 200 mg/kg body weight. The anti-inflammatory tests did not reveal significant therapeutic effects. However, the hypoazotemic tests demonstrated a reduction in blood urea and creatinine levels, and an increase in these indicators in urine, especially under conditions of acute renal failure, indicating a strong diuretic effect of the extracts. Conclusions. The Anemone nemorosa extracts exhibited strong hypoazotemic and diuretic activity, which may be beneficial for the treatment of kidney diseases. The absence of anti-inflammatory activity requires further analysis and possible modification of extraction methods. The study results support the potential use of this plant in developing new nephroprotective phytopreparations. © O. Khropot, Yu. Konechnyi, G. Lavryk, I. Tymchuk, O. Pinyazhko, V. Lubenets, R. Konechna.

Author keywords

Acute toxicity; Anemone nemorosa; Anti-inflammatory activity; Extracts; Hypoazotemic activity; Ranunculacea
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NOD2 C.3019-3020INSC AND C.2104C>T GENE VARIANTS AMONG PATIENTS FROM WESTERN UKRAINE WITH CROHN’S DISEASE AND COLORECTAL CANCER

Aim: To determine the frequency of NOD2 gene c.3019-3020insC (rs5743293) and c.2104C>T (rs2066844) allelic variants in the patients with Crohn’s disease (CD), colorectal cancer (CRC) and in the control groups and to study the association of these mutations with the onset time of the diseases, gender and surgical interventions. Materials and Methods: The diagnoses of CD and CRC were established based on standard clinical examination and laboratory tests. Molecular genetic study of a frameshift 3020insC mutations of NOD2 gene were performed in 54 patients with CD; missense R702W mutations of the NOD2 gene — in 41 CD patients and 38 healthy controls. In CRC group, 3020insC mutation was tested in 48 patients, R702W mutation — in 40 patients and 40 healthy controls. PCR-RFLP technique was used to identify the mutations. Results: The frequency of the minor allele (M) of 3020insC mutation of NOD2 gene in the patients with CD was significantly higher than in the control group (р = 0.01). The age at CD onset in females carrying 3020insC mutation was significantly lower (22.5 ± 1.6 years) when compared with females without the mutation (32.7 ± 2.5 years) (p = 0.002). There was no significant difference in the allele frequencies and genotype distributions of R702W mutation in the patients with CD in comparison with the controls. The mean age at CD onset in the patients carrying R702W mutation was significantly lower (28.4 ± 1.4 years) compared with the patients without the mutation (39.4 ± 2.8 years) (p < 0.01). Surgical interventions for CD was required in 40.0% of 3020insC mutation carriers. Among patients with CRC, only 4.2% carried 3020insC mutation and 20.0% R702W mutation. Our study suggests that R702W and 3020insC mutations are not associated with the risk of CRC in Ukrainian patients. There was no statistically significant difference in mean age at CRC onset in patients with/without R702W mutation. Only one patient with CRC had two mutations. Conclusion: The earlier age at CD onset was associated with 3020insC mutation, but only in female patients. The association between R702W mutation and the earlier age of CD onset was found. Patients with 3020insC mutation showed a trend to a higher frequency of surgical interventions for CD.
Key Words: 3020insC and R702W mutations of NOD2 gene, Crohn’s disease, colorectal cancer, disease onset, gender, surgical interventions.

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