The knee osteoarthritis susceptibility locus DVWA on chromosome 3p24.3 is the 5′ part of the split COL6A4 gene

In a recent study the DVWA gene located on human chromosome 3p24.3 was identified as a susceptibility locus for knee osteoarthritis in Japanese and Chinese patients (Miyamoto, Y., Shi, D., Nakajima, M., Ozaki, K., Sudo, A., Kotani, A., Uchida, A., Tanaka, T., Fukui, N., Tsunoda, T., Takahashi, A., Nakamura, Y., Jiang, Q., Ikegawa, S., 2008. Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. Nat. Genet. 40, 994–998). The authors concluded that DVWA codes for a novel protein containing two von Willebrand factor A (VWA) domains without a signal peptide sequence. The experimental data provided in this interesting study led to the suggestion of a mechanism for the etiology of the disease, based on an interaction between DVWA protein and β-tubulin. More recently, no significant association between DVWA and osteoarthritis was found in UK patient samples (Valdes, A.M., Spector, T.D., Doherty, S., Wheeler, M., Hart, D.J., Doherty, M., 2008. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann. Rheum. Dis. Dec 3. [Epub ahead of print]), but a meta-analyses with data from individuals of white European descent from the Netherlands, the UK, Spain and Greece and the original Japanese and Chinese cohort provided evidence for a global association of one of the polymorphisms, a cysteine to tyrosine exchange (rs7639618) (Meulenbelt, I., Chapman, K., Dieguez-Gonzalez, R., Shi, D., Tsezou, A., Dai, J., Malizos, K.N., Kloppenburg, M., Carr, A., Nakajima, M., van der Breggen, R., Lakenberg, N., Gomez-Reino, J.J., Jiang, Q., Ikegawa, S., Gonzalez, A., Loughlin, J., Slagboom, E.P., 2009. Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations. Hum. Mol. Genet. 8, 1518–1523). However, there was no independent association with knee osteoarthritis in Europeans. Here we present information that the newly identified DVWA represents the human gene coding for the collagen VI α4 chain, which could point to a more complex disease mechanism.