GENDER DIFFERENCES IN THE ASSOCIATION BETWEEN rs1899663 LONG NON-CODING RNA HOTAIR GENE POLYMORPHISM AND KIDNEY CANCER DEVELOPMENT

Volkogon A. D., Obukhova O. A., Harbuzova V. Yu., Ataman A. V.

MEDICAL GENETICS

Scentific article

HOX antisense intergenic RNA (HOTAIR), the well-studied long noncoding RNA (lnRNA), realizes the regulation of cell cycle genes expression at the epigenetic and transcriptional levels. The results of experiments showed that HOTAIR promotes epithelial-mesenchymal transition (EMT) during the renal-cell carcinoma (RCC) development. Moreover, HOTAIR knockdown inhibits proliferation and invasion of RCC cells. At the same time the role of HOTAIR gene polymorphisms in kidney cancer development is unknown. The aim of the study was to perform a case-control study on representatives of both genders in order to assess the possible link between HOTAIR rs1899663 gene polymorphism and kidney cancer development in Ukrainian population. Object and methods. 141 unrelated Ukrainian patients (42 female, 59 male) with clear cell renal cell carcinoma (CCRCC) and 100 healthy subjects (34 female, 56 male) were enrolled to case-control study. HOTAIR rs1899663 polymorphism genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The mathematical processing of obtained results was done using Statistical Package for Social Science software (SPSS, version 17.0, Chicago, IL, USA). All statistical tests were two-sided, P <0.05 was considered significant. Results. It was shown that ratio of HOTAIR rs1899663 GG-, GT- and TT-genotypes between CCRCC patients and control subjects did not differ (P = 0.207). Comparison of rs1899663 genotype frequencies in groups of different sex demonstrated no significant difference between CCRCC patients and control group in women (P = 0.067) and men (P = 0.248). The results of logistic regression analysis showed the association between HOTAIR rs1899663 polymorphic locus and CCRCC occurrence in female subjects under superdominant model of inheritance. Women with GT-genotype had 2.7 times increased risk of kidney cancer development compared to women with GG- and TTgenotypes (95% СІ = 1.058-6.868; Р = 0.038). The link between HOTAIR rs1899663 gene polymorphism and CCRCC development in male subjects was not found in any inheritance model (P > 0.05). Conclusion. Obtained results revealed that long non-coding RNA HOTAIR rs1899663 polymorphic site was associated with kidney cancer development only in female Ukrainian patients. The risk of CCRCC occurrence in women with GT-genotype was higher than in women with GG- and TT-genotypes.

long non-coding RNA, HOTAIR, gene polymorphism, kidney cancer

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«Bulletin of problems biology and medicine» Issue 1 Part 2 (149), 2019 year, 221-224 pages, index UDK 616.6-006:577.213/.216

10.29254/2077-4214-2019-1-2-149-221-224