Association of HOTAIR gene polymorphisms and biochemical markers to uterine fibroids in Egyptian women.

Background Uterine fibroids (UFs) are the most common benign tumors of the female reproductive system, with a multifactorial etiology involving genetic, hormonal, and inflammatory mechanisms. Long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) has been implicated in tumorigenesis; however, the role of its genetic polymorphisms in uterine fibroids remains insufficiently explored. Aim This study aimed to investigate the association between HOTAIR gene polymorphisms (rs1899663, rs12826786, and rs4759314) and susceptibility to uterine fibroids in Egyptian women, as well as their relationship with inflammatory, hormonal, and biochemical parameters. Methods A total of 200 participants were enrolled, including 100 uterine fibroid patients and 100 age-matched healthy controls. Genotyping of HOTAIR polymorphisms was performed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Serum cytokines, hormonal markers, and biochemical parameters were measured using ELISA and standard clinical methods. Statistical analyses were conducted to evaluate genotype–phenotype associations and disease risk. Results The rs12826786 polymorphism showed a significant association with uterine fibroid susceptibility, with the T allele being more frequent in patients than controls (45.5% vs. 33.5%, OR = 1.657, p = 0.019). Significant associations were also observed under the dominant and codominant genetic models ( p = 0.026). In contrast, rs1899663 and rs4759314 polymorphisms showed no significant association. Uterine fibroid patients exhibited significantly elevated levels of inflammatory cytokines (IL-1β, IL-10, TNF-α, IFN-γ), hormonal markers (prolactin and estradiol), and liver enzymes (ALT, AST, ACP), along with decreased total protein and albumin levels ( p < 0.001). A significant association between rs12826786 and ALT levels was also observed ( p = 0.038). Principal component analysis demonstrated clustering patterns influenced by inflammatory and hormonal parameters. Conclusion This study demonstrates that the HOTAIR rs12826786 polymorphism is significantly associated with increased susceptibility to uterine fibroids in Egyptian women, potentially through modulation of inflammatory and hormonal pathways. These findings highlight the potential role of lncRNA polymorphisms as biomarkers for uterine fibroid risk. However, further studies in larger and diverse populations are required to validate these findings.