Association of ANO6 gene polymorphism and expression with ankylosing spondylitis in a Chinese Han population

Introduction This study aimed to explore the genetic polymorphisms and aberrant expression of Anoctamin 6 (ANO6) in Ankylosing Spondylitis (AS) patients to understand its role in AS pathogenesis. Material and methods Genetic sequencing was performed to identify disease-associated single nucleotide polymorphisms (SNPs) within the exonic and transcriptional regulatory regions of ANO6 in 417 AS patients and 541 healthy controls (HCs). Linkage disequilibrium and haplotype analyses were conducted to assess the association of the candidate SNPs with disease susceptibility. A cohort of 2,144 AS patients was stratified based on the presence or absence of risk-associated haplotypes and clinical phenotypes were compared between the two groups. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to quantify mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 40 AS patients and 32 HCs. Immunohistochemistry (IHC) was utilized to evaluate ANO6 protein expression in tendon tissues from 9 AS patients and 5 control subjects. Results Five SNP loci (rs79662606, rs76186361, rs17095830, rs80224086, and rs75712006) exhibited significant associations with AS susceptibility, with strong linkage disequilibrium observed between pairwise loci. Haplotype analysis revealed a higher prevalence of GTGCG, ATGTA, and ACGTA haplotypes in AS patients (p < 0.001). No significant differences in clinical phenotypes were observed between AS patients with or without risk-associated haplotypes. mRNA expression in PBMCs was significantly lower in AS patients (0.49 ± 0.21) compared to HCs (0.86 ± 0.38) (p < 0.001). Conversely, ANO6 protein expression was significantly elevated in tendon tissues of AS patients, with an average Histoscore of 182.22 ± 30.732 compared to 62.00 ± 35.637 in controls (p = 0.001). Conclusions ANO6 may represent a novel AS susceptibility gene, with GTGCG, ATGTA, and ACGTA as risk-associated haplotypes. Dysregulated ANO6 expression in PBMCs and tendon tissues suggests its potential role in AS pathogenesis.