DIRC3 and carpal tunnel syndrome: In the present study, the protective T allele at our putative causal SNP had tissue-specific effects on expression of DIRC3 and IGFBP5. In both skin fibroblasts and operative tenosynovium samples from patients with carpal tunnel syndrome, the protective allele was associated with enhanced expression of IGFBP5. IGFBP5 is a highly conserved and multifunctional secreted protein that binds to IGF and can have complex and varying effects on IGF signalling depending on the tissue type and context.