ANALYSIS OF ASSOCIATION BETWEEN ANRIL GENE POLYMORPHISM AND KIDNEY CANCER DEVELOPMENT IN SMOKERS
About the author:
Volkogon A. D., Obukhova O. A., Harbuzova V. Yu., Ataman O. V
Type of article:
ANRIL (Antisense Non-coding RNA in the INK4 Locus, also known as CDKN2B-AS1) – 3.8-kb long non-coding RNA transcribed from the antisense strand of INK4b-ARF-INK4a gene cluster. It is known that ANRIL overexpression is associated with development of oncological pathologies of different localization. In addition, there are a number of studies devoted to role of ANRIL genetic polymorphism in emergence and progression of tumors, including tumors of genitourinary system.The aim of the study was to establish a possible association between rs4977574 ANRIL gene polymorphism and clear cell renal cell carcinoma (CCRCC) development in representatives of Ukrainian population which are smokers and non-smokers. Object and methods. Whole venous blood of 101 patients with CCRCC (42 women and 59 men) and 100 patients without oncopathology history (34 women and 66 men) was used in the study. DNA from blood white cells was extracted using GeneJET Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific, USA). Genotyping of rs4977574 ANRIL gene polymorphic locus was performed using real-time polymerase chain reaction (real-time PCR) method in the presence of TaqMan assay C_31720978_30. The mathematical data were processed using the SPSS software package (version 17.0). P values < 0.05 were considered as statistically significant. Results. It was found that difference in rs4977574-genotype distribution between patients with CCRCC and control persons was absent in general group (P = 0.216). At the same time, the statistical analysis stratified by smoking showed that both in non-smokers and smokers rs4977574-genotypes frequency also did not differ significantly between comparison groups (P = 0.511 and P = 0.099, respectively). However, after adjusting for age, gender, body mass index, and smoking habits statistically significant association between rs4977574 ANRIL gene polymorphism and risk of kidney cancer development was detected in smokers subjects under superdominant inheritance model (P = 0.043). It was revealed that heterozygotes (AG-genotype) have 2.85-fold higher risk of CCRCC development (95% CI = 1.003-7.884) compared to smokers with AA- and GG-genotypes. Conclusion. The rs4977574 ANRIL gene polymorphism is related to risk of kidney cancer development only in smokers. Smokers with rs4977574AG-genotype have higher risk of kidney cancer emergence compared to rs4977574AA- and rs4977574GG-homozygotes.
long non-coding RNA, ANRIL, gene polymorphism, kidney cancer, smoking.
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Publication of the article:
«Bulletin of problems biology and medicine» Issue 4 Part 1 (153), 2019 year, 174-177 pages, index UDK 616.6-006:577.213/.216