{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T12:36:15Z","timestamp":1774787775610,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,3,2]],"date-time":"2012-03-02T00:00:00Z","timestamp":1330646400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A genome-wide association scan with subsequent replication study that involved over 67,000 individuals of European ancestry has produced evidence of association of single nucleotide polymorphism rs2277831 to primary osteoarthritis (OA) with a P-value of 2.9 \u00d7 10<jats:sup>-5<\/jats:sup>. rs2277831, an A\/G transition, is located in an intron of<jats:italic>MICAL3<\/jats:italic>. This gene is located on chromosome 22q11.21 and the association signal encompasses two additional genes,<jats:italic>BCL2L13<\/jats:italic>and<jats:italic>BID<\/jats:italic>. It is becoming increasingly apparent that many common complex traits are mediated by<jats:italic>cis<\/jats:italic>-acting regulatory polymorphisms that influence, in a tissue-specific manner, gene expression or transcript stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used total and allelic expression analysis to assess whether the OA association to rs2277831 is mediated by an influence on MICAL3, BCL2L13 or BID expression. Using RNA extracted from joint tissues of 60 patients who had undergone elective joint replacement surgery, we assessed whether rs2277831 correlated with allelic expression of either of the three genes by: 1) measuring the expression of each gene by quantitative PCR and then stratifying the data by genotype at rs2277831 and 2) accurately discriminating and quantifying the mRNA synthesised from the alleles of OA patients using allelic-quantitative PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found no evidence for a correlation between gene expression and genotype at rs2277831, with P-values of 0.09 for<jats:italic>BCL2L13<\/jats:italic>, 0.07 for<jats:italic>BID<\/jats:italic>and 0.33 for<jats:italic>MICAL3<\/jats:italic>. In the allelic expression analysis we observed several examples of significant (p &lt; 0.05) allelic imbalances, with an allelic expression ratio of 2.82 observed in<jats:italic>BCL2L13<\/jats:italic>(P = 0.004), 2.09 at<jats:italic>BID<\/jats:italic>(P = 0.001) and the most extreme case being at<jats:italic>MICAL3<\/jats:italic>, with an allelic expression ratio of 5.47 (P = 0.001). However, there was no correlation observed between the pattern of allelic expression and the genotype at rs2277831.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In the tissues that we have studied, our data do not support our hypothesis that the association between rs2277831 and OA is due to the effect this SNP has on<jats:italic>MICAL3, BCL2L13<\/jats:italic>or<jats:italic>BID<\/jats:italic>gene expression. Instead, our data point towards other functional effects accounting for the OA associated signal.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2350-13-12","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T14:53:07Z","timestamp":1330959187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3"],"prefix":"10.1186","volume":"13","author":[{"given":"Madhushika","family":"Ratnayake","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise N","family":"Reynard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma VA","family":"Raine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Santibanez-Koref","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Loughlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,3,2]]},"reference":[{"key":"934_CR1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.rdc.2008.05.011","volume":"34","author":"KD Brandt","year":"2008","unstructured":"Brandt KD, Dieppe P, Radin EL: Etiopathogenesis of osteoarthritis. 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