Variation of the encoding hyaluronic receptors Hyaluronan-mediated motility receptor (rs299295) and Stabilin-2 (rs2271637) genes with prostate neoplasms risk: A case-control and in silico study.

Abstract

Background: Hyaluronan-mediated motility receptor (HMMR) and Stabilin-2 (STAB2), known as extracellular matrix cell surface protein's receptors, bind to hyaluronic acid and lead to various cell functions.

Objective: The study aims to investigate the relationship between the HMMR-rs299295 (C $>$ T/ A485V) and STAB2-rs2271637 (C $>$ G/ L2401V) gene variants and the risk of prostate neoplasms in the Mazandaran population, North of Iran.

Materials and methods: This study was conducted based on a case-control and in silico approach. Genomic DNA was extracted from 598 intravenous blood samples, collected from 250 benign prostatic hyperplasia (case group I) and 250 malignant prostate (case group II) neoplasms as cases, and 98 healthy men as control. The HMMR-rs299295 and STAB2-rs2271637 genotypes were identified using the polymerase chain reaction-restriction fragment length polymorphism method. Bioinformatics analyses were conducted using PolyPhen-2, GOR IV, and GeneMANIA free web tools.

Results: The study found that the mutant T allele in HMMR-rs299295 and the G allele in STAB2-rs2271637 are associated with an increased risk of prostate neoplasm, including benign prostatic hyperplasia and prostate cancer (p $<$ 0.001). Bioinformatic analyses revealed structural changes and potential damage from these variants. The HMMR-A485V variant might impair interaction with family with sequence similarity 83 member D, and the STAB2-L2401V variant could disrupt domain 7 of FAS1, together they may affect the protein's physical interactions, especially with mitogen-activated protein kinase 1.

Conclusion: The mutant alleles of T in HMMR-rs299295 and the G in STAB2-rs2271637 may disrupt protein structures and probably contribute to prostate neoplasm progression.