allelic expression analysis of the osteoarthritis susceptibility locus that maps to mical3骨关节炎易感位点的等位基因表达分析,映射到mical3.pdfVIP

Ratnayake et al. BMC Medical Genetics 2012, 13:12 /1471-2350/13/12 RESEARCH ARTICLE Open Access Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3 1 1 1 2 1* Madhushika Ratnayake , Louise N Reynard , Emma VA Raine , Mauro Santibanez-Koref and John Loughlin Abstract Background: 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 × 10-5. rs2277831, an A/G transition, is located in an intron of MICAL3. This gene is located on chromosome 22q11.21 and the association signal encompasses two additional genes, BCL2L13 and BID. It is becoming increasingly apparent that many common complex traits are mediated by cis-acting regulatory polymorphisms that influence, in a tissue-specific manner, gene expression or transcript stability. Methods: 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. Results: We found no evidence for a correlation between gene expression and genotype at