To investigate the effect in OA (Osteoarthritis) susceptibility of putative damaging changes in ADAM (A Disintegrin And Metalloprotease) and ADAMTS (ADAM with ThromboSpondin motif) proteases.
Non-synonymous single nucleotide polymorphisms (nsSNP) in 18 ADAMTS and 31 ADAM genes were analyzed with two software applications for prediction of functional damage. Four putative damaging nsSNP were found in ADAMTS2, ADAMTS14, ADAMTS16 and ADAM12, respectively. These nsSNPs were analyzed in case-control sample collections with a variety of phenotypes totalling 3217 OA patients and 2214 healthy controls, all of them Caucasians.
No statistically significant differences were found in ADAMTS2, ADAMTS16 and ADAM12 nsSNPs. Conversely, the rare allele of the rs4747096 nsSNP in ADAMTS14 was overrepresented in women requiring joint replacement because of knee OA (O.R.(M-H) (odds ratio. Mantel-Haenszel)=1.41, 95% C.I.=1.1-1.8; P=0.002) and in patients with symptomatic hand OA (O.R.=1.37, 95% C.I.=1.0-1.9; P=0.047). A non significant increase in the frequency of the same allele was also found in patients with hip OA requiring prosthesis (O.R.(M-H)=1.14, 95% C.I.=1.0-1.3; P=0.08). No association was found with other OA phenotypes.
Our findings implicate ADAMTS14 in OA, specifically in knee OA requiring joint replacement in women and, possibly, in hand OA. Independent association of ADAMTS14 genetic variation to knee OA in women has been communicated. ADAMTS14 involvement, if confirmed, will open a new area of interest in OA pathogenesis because of its role in the maturation of collagen fibers.