rs3204689

Shepherd et al. characterized the functional basis of the ALDH1A2 genetic association with osteoarthritis, identifying rs12915901 as a key target variant that affects retinoic acid pathway function. Using RNA-seq, allelic expression imbalance analysis, ALDH1A2 knockdown, and transcription factor binding assays in chondrocytes and joint tissues, they demonstrate that the risk allele impairs ALDH1A2 expression and downstream retinoic acid signaling. The study links rs12915901 and related variants to altered chondrogenic gene expression patterns implicated in osteoarthritis pathogenesis.

Candidate gene study of 4 SNPs in Russian population replicating GWAS-significant variants associated with stage 4 knee osteoarthritis. The A allele of rs6499244 in NFAT5 was identified as a risk factor for knee osteoarthritis in additive (OR=1.61, p=0.02) and recessive (OR=2.07, p=0.02) models. Functional analysis shows rs6499244 is located in DNase-hypersensitive regions and enhancers, associated with expression of 9 genes including NFAT5 itself.