Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1

作者：Gee Fiona^*; Clubbs Clare F; Raine Emma V A; Reynard Louise N; Loughlin John

来源：BMC Medical Genetics, 2014, 15(1): 53.

DOI：10.1186/1471-2350-15-53

• Osteoarthritis
• Genetic risk
• Single nucleotide polymorphism
• Allelic imbalance
• Linkage disequilibrium

Background: An osteoarthritis (OA) susceptibility locus has been mapped to chromosome 3p21, to a region of high linkage disequilibrium encompassing twelve genes. Six of these genes are expressed in joint tissues and we therefore assessed whether any of the six were subject to cis-acting regulatory polymorphisms active in these tissues and which could therefore account for the association signal.
Methods: We measured allelic expression using pyrosequencing assays that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism. We assessed RNA extracted from the cartilage and other joint tissues of OA patients who had undergone elective joint replacement surgery. A two-tailed Mann-Whitney exact test was used to test the significance of any allelic differences.
Results: GNL3 and SPCS1 demonstrated significant allelic expression imbalance (AEI) in OA cartilage (GNL3, mean AEI = 1.04, p = 0.0002; SPCS1, mean AEI = 1.07, p < 0.0001). Similar results were observed in other tissues. Expression of the OA-associated allele was lower than that of the non-associated allele for both genes.
Conclusions: cis-acting regulatory polymorphisms acting on GNL3 and SPCS1 contribute to the OA association signal at chromosome 3p21, and these genes therefore merit further investigation.

• 出版日期2014-5-4