THE IMPACT OF BODY MASS INDEX ON ASSOCIATION BETWEEN ANRIL GENE POLYMORPHISM AND RENAL CELL CARCINOMA DEVELOPMENT

The aim of the study was to investigate the association between rs4977574 polymorphism of the long non-coding RNA ANRIL gene and renal cell carcinoma development depending on body mass index (BMI). Materials and methods of the research. The venous blood of 101 patients with clear cell renal cell carcinoma (CCRCC) and 100 individuals without cancer history was used for the study. Venous blood leukocyte DNA was ex-tracted using commercial GeneJET Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific, USA). Genotyping of ANRIL gene rs4977574 polymorphism was performed by Real-time PCR method using TaqMan assay C_31720978_30. The reaction was performed on Quant Studio 5 DX Real-Time (Applied Biosystems, USA). Obtained data was analyzed using SPSS software package (version 17.0). The mean values between two groups were compared using Student's t-test, between three groups – using one-way ANOVA followed by Bonferroni post-hoc test. The risk of CCRCC onset depending on particular rs4977574-genotype was calculated using binary and multivariate logistic regression under different models of inheritance. P values < 0.05 were considered as statistically significant. Results of research. The analysis of results in total sample showed no difference in rs4977574-genotypes dis-tribution between control and cancer groups (P = 0.216). This difference was almost significant (P = 0.053) in individu-als with BMI < 25 kg/m2. However, in persons with BMI ≥ 25 kg/m2 the rs497757-genotypes frequency was signifi-cantly different between patients with renal cancer and control subjects (P = 0.002). It was revealed that minor allele G has a protective effect for CCRCC occurrence in subjects with BMI < 25 kg/m2 (OR = 0.300; P = 0.045 – for dominant model of inheritance). Significant results were also preserved after adjusting for sex, age and smoking habit (OR = 0.169; P = 0.031). The analysis of overweight individuals showed that the minor G-allele of ANRIL gene rs4977574 polymorphism, on the contrary, increased the CCRCC risk (OR = 4,552; P = 0.001 – for dominant model; OR = 2.036; P = 0.041 – for super-dominant model). The statistical significance of results was also maintained after adjusting for sex, age and smoking (OR = 4.202; P = 0.030 – for dominant model; OR = 3.785; P = 0.023 – for super-dominant mod-el). It was also found that BMI (27.5 ± 4.2 kg/m2) in CCRCC patients with minor G-allele (genotypes AG and GG) was higher compared to AA-homozygotes (25. 2 ± 4.3 kg/m2; P = 0.028). Conclusions. BMI affects the nature of association between ANRIL gene rs4977574 polymorphism and CCRCC development. Thus, the minor G-allele reduces the CCRCC risk in persons with normal weight. However, in persons with overweight, G-allele is associated with increased CCRCC risk. Also, there is link between ANRIL gene rs4977574 polymorphism and BMI in CCRCC patients. The BMI in minor G-allele carriers is higher compared to AA-homozygotes.