Analysis of the GSTP1 rs1695 polymorphism association with the development of asthma and phenotypic manifestations.

OBJECTIVE: The development of asthma and its related phenotypes is most likely due to the polymorphism of the so-called modifier genes. The goal of this study was to evaluate the polymorphic locus rs1695 of the GSTP1 gene association with risk factors for developing asthma and its phenotypic manifestations. METHODS: This case-control study involved 164 patients with confirmed asthma diagnosis and 147 age- and sex-matched controls. Patients were divided into two groups: with (n = 121) and without complications (n = 43). Among asthmatic patients, 34 manifested hypersensitivity to household allergens. The GSTP1 rs1695 polymorphism was genotyped using the technique of polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences between patients and controls in allelic or genotype frequencies of polymorphic locus rs1695 of the GSTP1 gene. However, the frequency of the A/A genotype in the patient group with complications was significantly lower than that in complication-free patients (p = 0.040), while the frequency of the G allele was higher in patients with complications (p = 0.030). The frequency of the A/A genotype was decreased in the patient group with an allergic reaction to household allergens in comparison with controls (p = 0.037). CONCLUSION: These results suggest that the carriage of the A/A genotype of polymorphic locus rs1695 of the GSTP1 gene is a protective factor in the development of complications and an allergic reaction to house allergens among asthmatics, while the carriage of the G allele is associated with an increased risk for asthma complications.

Genetic Polymorphisms of Cytochromes P450 in Finno-Permic Populations of Russia.

Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, endogenous hormones, and drugs, including those used in COVID-19 treatment. Cytochrome p450 genes are linked to the pathogenesis of some multifactorial traits and diseases, such as cancer, particularly prostate cancer, colorectal cancer, breast cancer, and cervical cancer. Genotyping was performed on 540 supposedly healthy individuals of 5 Finno-Permic populations from the territories of the European part of the Russian Federation. There was a statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; data on the rs3892097 locus of the CYP2D6 gene shows that Izhemsky Komis are different from the Mordovian and Udmurt populations.

A Splice Site Variant of CDK12 and Breast Cancer in Three Eurasian Populations.

CDK12 is a member of the cyclin-dependent kinase family that acts as regulator of DNA damage response gene expression. A c.1047-2A>G splice site variant of the CDK12 gene was recently reported to strongly associate with hereditary breast and ovarian cancer in patients of Tatar ethnic origin. To gain more insight into the potential risk and the population spread of the c.1047-2A>G variant, we have genotyped three breast cancer case-control series of Tatar, Bashkir and Kazakh ethnicity. We identified c.1047-2A>G in 6/155 cases and 12/362 controls of Tatar ancestry, 0/96 cases and 9/189 controls of Bashkir ancestry, and 1/131 cases and 0/154 controls of Kazakh ancestry (Mantel-Haenszel odds ratio 0.72, 95% CI 0.30-1.70, p = 0.45). Consistent with the absence of a large effect, bioinformatic analyses predicted that c.1047-2A>G modulates alternative splicing of a NAGNAG sequence rather than constituting a loss-of-function allele, and RT-PCR analyses of c.1047-2A>G heterozygous lymphocytes verified the usage of the predicted alternative acceptor site. Our study confirms a high prevalence of CDK12*c.1047-2A>G in the Tatar and Bashkir population but excludes a role as a clinically actionable high-risk breast cancer mutation.