HOTAIR lncRNA variants are associated with psoriasis susceptibility: A case-control study

BACKGROUND: Psoriasis is a chronic, immune-mediated skin disease characterized by keratinocyte hyperproliferation and persistent inflammation. Recent studies suggest that long non-coding RNAs (lncRNAs), such as HOX transcript antisense RNA (HOTAIR), may play critical roles in regulating inflammatory pathways involved in psoriasis pathogenesis. OBJECTIVES: This study aimed to investigate the association between HOTAIR gene polymorphisms (rs12826786 and rs4759314) and psoriasis susceptibility, and to assess their potential regulatory effects on gene expression using expression quantitative trait loci (eQTL) data. MATERIAL AND METHODS: A case-control study including 158 patients with psoriasis and 153 controls was conducted. Genotyping of rs12826786 and rs4759314 was performed using the tetra-primer amplification refractory mutation system (T-ARMS) polymerase chain reaction (PCR). Primary associations were tested using multivariable logistic regression in an additive (per-allele) model, adjusting for sex, age in tertiles (T1 reference), smoking, and comorbidity; dominant and genotypic (3-level) models were secondary. Expression quantitative trait loci data from publicly available databases were analyzed to explore the impact of these polymorphisms on HOTAIR expression in skin tissue. RESULTS: Under a multivariable additive model (adjusted for sex, age tertiles, smoking, and comorbidity), rs12826786 was associated with higher odds of psoriasis (odds ratio (OR) = 1.52, 95% confidence interval (95% CI): 1.11-2.08; q = 0.027) and rs4759314 likewise (OR = 1.73, 95% CI: 1.18-2.53; q = 0.020). Dominant contrasts were also significant: rs12826786 (CT + TT vs CC: OR = 1.84, 95% CI: 1.12-3.05; q = 0.027) and rs4759314 (AG + GG vs AA: OR = 2.03, 95% CI: 1.18-3.48; q = 0.020). Expression quantitative trait loci analysis revealed that the rs12826786 T allele significantly upregulates HOTAIR expression in both sun-exposed and non-sun-exposed skin (both p < 0.001). CONCLUSIONS: HOTAIR polymorphisms, particularly rs12826786 and rs4759314, are associated with psoriasis risk and may contribute through regulation of HOTAIR expression. These findings support HOTAIR as a potential biomarker and therapeutic target in psoriasis.