association of hnf1b-rs4794758 and lmtk2-rs7791463 gene variants with prostate neoplasia risk: case-control and bioinformatics studies

Prostate neoplasms, such as prostate cancer and benign prostatic hyperplasia, are complex and heterogeneous diseases that are caused by environmental, metabolic, and genetic factors. various reports showed the relationship of several genes, including the hnf1b and lmtk2 genes, in the occurrence of prostate cancer. this study investigated the association of hnf1b-rs4794758 and lmtk2-rs7791463 polymorphisms with prostate cancer and benign prostatic hyperplasia in a case-control study, followed by bioinformatics analysis. for this purpose, blood samples were collected from 70 healthy men, 58 men with benign prostatic hyperplasia (positive digital rectal examination or dre and psa levels below 4 ng/ml), and 70 men with prostate cancer (positive dre, psa levels above 4 ng/ml, and diagnoses confirmed by pathological findings). these men were referred to shahid beheshti hospital in babol. after genomic dna extraction, the genotype was determined using pcr-rflp. a genotypic and allelic analysis revealed that the rs4794758 polymorphism with aa genotype (or: 4.808, 95%ci: 1.260-18.348, p= 0.022) had a significant difference between the prostate cancer group and the benign prostatic hyperplasia group compared to the control group. allele a of this polymorphism was also significantly associated with prostate cancer (or: 1.705, 95%ci: 1.055-2.755, p= 0.030). however, there was no correlation between different genotypes of the rs7791463 polymorphism with prostate cancer and benign prostatic hyperplasia. bioinformatics analysis by some online servers and software showed that the rs4794758 polymorphism possibly changes the hnrna splicing pattern. so, this polymorphism could probably provide a locus for the tbp transcription factor. in addition, the rs7791463 polymorphism potentially alters the hnrna splicing pattern and changes the reading frame. based on the data, hnf1b-rs4794758 polymorphism is associated with prostate cancer susceptibility, which can be considered a molecular risk factor in future studies.