| Title: |
Dissect Gender-Dependent Susceptibility SNPs in Progressive Osteoarthritis Using Regulator Motif Candidate of Genetic Association Strategy (RMCGA) |
| Authors: |
Yin-Shiuan Bai; Ding-Lian Wang; Meng-Chang Lee; Chih-Chien Wang; Wen-Hui Fang; Su-Wen Chuang; Yu-Hsuan Chen; Hao Su; Cheng-Jung Chen; Sui-Lung Su |
| Source: |
International Journal of Molecular Sciences ; Volume 26 ; Issue 9 ; Pages: 4117 |
| Publisher Information: |
Multidisciplinary Digital Publishing Institute |
| Publication Year: |
2025 |
| Collection: |
MDPI Open Access Publishing |
| Subject Terms: |
gender-specific; osteoarthritis (OA); NF-κB binding sites; single nucleotide polymorphisms (SNPs) |
| Subject Geographic: |
agris |
| Description: |
The role of gender in osteoarthritis (OA) has been reported. However, knowledge on whether gender-specific regulatory SNPs are determining factors in OA is limited. We aimed to identify susceptible gender-specific SNPs of transcription factor binding sites in OA. We used a modified NF-κB binding motif from an RNA sequencing data-inferred OA-associated upstream regulator to define genome-wide potential NF-κB binding sites, which were aligned to the Taiwan BioBank SNP database to identify susceptible SNPs. A case-control study was conducted to verify SNPs with OA determined by a logistic model. The functional assessment was validated using the Genotype-Tissue Expression Portal database. We collected 533 OA patients and 614 healthy controls. Two of nine novel OA-associated SNPs were identified to be significant. For males, the variant of rs73164856 in the aldose reductase gene enhancer was identified to be a protective factor of severe OA patients [odds ratio (OR): 0.17, 95% confidence interval (CI): 0.04–0.73]. For females, the variant of the rs545654 in the neuronal NOS (nNOS) gene was identified to be a detrimental factor of severe OA patients (OR: 2.07, 95% CI: 1.15–3.73). The gene expression analysis demonstrated a lower expression of the AKR1B15 gene (p = 0.00019) upon the rs73164856 T allele; meanwhile, it showed a higher expression of the nNOS gene (p = 1.2 × 10−17) upon the rs545654 T allele. This study identifies susceptible gender-specific SNPs of NF-κB binding sites in severe OA and validates the RMCGA, which sheds light on genetic determinants by gender in advanced OA. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms26094117 |
| DOI: |
10.3390/ijms26094117 |
| Availability: |
https://doi.org/10.3390/ijms26094117 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.119B1E36 |
| Database: |
BASE |