A SNP (rs12901499) mapping to intron 1 of SMAD3 was associated with both knee and hip OA (P < 0.0022 and P < 0.021, respectively) in the discovery set.
Associations were observed between tissue non-specific alkaline phosphatase (TNAP), osteocalcin (OCN), TWIST1, TGFβ1, SMAD3 mRNA levels and mineral measures in OA against CTL.
A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10<sup>-10</sup>, OR = 1.08, p.Pro1284Leu).
Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89).
And the pooled results revealed significant association between SMAD3rs12901499 polymorphism and both knee and hip OA (knee OA: OR 1.18, 95% CI 1.04-1.34; hip OA: OR 1.31, 95% CI 1.18-1.44).
COMP and FAC are specific biomarkers with potential utility in the diagnosis and management of FAI and hip OA, given their ability to differentiate between controls and patients with hip lesions.
The discovery of a novel variant near the NCOA3 (nuclear receptor coactivator 3) gene associated with hip OA and the regulation of GDF5 gene by four transcription factors via the OA susceptibility locus rs143383 are among important findings in OA genetics.
A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations.
On the basis of this premise and in the light of the finding in a small observational study that HFE gene mutations are very common in precocious bilateral hip OA (100% amongst 8 sequentially collected patients), it is hypothesised that precocious bilateral hip OA is a "form-fruste" of the arthropathy of HH in which HFE gene mutation mediated articular iron deposition in hip joint tissues may be of pivotal pathogenetic importance.
Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10<sup>-12</sup>, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10<sup>-11</sup>, rs4252548" genes_norm="3589">p.Arg112His).
Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10<sup>-12</sup>, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10<sup>-11</sup>, rs4252548" genes_norm="3589">p.Arg112His).
In cartilage, however, the mRNA expression of the inflammatory cytokines and the catabolic genes MMP-13 and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) was higher in the FAI samples compared with the OA samples (p < 0.01).
Transforming growth factor-β1 (TGF-beta1) and interleukin-6 (IL-6) are included in pathogenesis of OA, as well as in development of the musculoskeletal system.
Transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) are two pro-inflammatory cytokines included in pathogenesis of OA, bone remodeling and development of bone and joint tissues.
Associations were observed between tissue non-specific alkaline phosphatase (TNAP), osteocalcin (OCN), TWIST1, TGFβ1, SMAD3 mRNA levels and mineral measures in OA against CTL.