Variation of the encoding hyaluronic receptors Hyaluronan-mediated motility receptor (rs۲۹۹۲۹۵) and Stabilin-۲ (rs۲۲۷۱۶۳۷) genes with prostate neoplasms risk: A case-control and in silico study

Background: Hyaluronan-mediated motility receptor (HMMR) and Stabilin-۲ (STAB۲), 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-rs۲۹۹۲۹۵ (C>T/ A۴۸۵V) and STAB۲-rs۲۲۷۱۶۳۷ (C>G/ L۲۴۰۱V) 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 ۵۹۸ intravenous blood samples, collected from ۲۵۰ benign prostatic hyperplasia (case group I) and ۲۵۰ malignant prostate (case group II) neoplasms as cases, and ۹۸ healthy men as control. The HMMR-rs۲۹۹۲۹۵ and STAB۲-rs۲۲۷۱۶۳۷ genotypes were identified using the polymerase chain reaction-restriction fragment length polymorphism method. Bioinformatics analyses were conducted using PolyPhen-۲, GOR IV, and GeneMANIA free web tools. Results: The study found that the mutant T allele in HMMR-rs۲۹۹۲۹۵ and the G allele in STAB۲-rs۲۲۷۱۶۳۷ are associated with an increased risk of prostate neoplasm, including benign prostatic hyperplasia and prostate cancer (p < ۰.۰۰۱). Bioinformatic analyses revealed structural changes and potential damage from these variants. The HMMR-A۴۸۵V variant might impair interaction with family with sequence similarity ۸۳ member D, and the STAB۲-L۲۴۰۱V variant could disrupt domain ۷ of FAS۱, together they may affect the protein's physical interactions, especially with mitogen-activated protein kinase ۱. Conclusion: The mutant alleles of T in HMMR-rs۲۹۹۲۹۵ and the G in STAB۲-rs۲۲۷۱۶۳۷ may disrupt protein structures and probably contribute to prostate neoplasm progression.

کلیدواژه ها:

FAM۸۳D ، Fasciclin-like ، HMMR ، MAPK۱ ، Prostate neoplasm ، STAB۲. ، FAM۸۳D ، Fasciclin-like ، HMMR ، MAPK۱ ، نئوپلاسم پروستات ، STAB۲.