期刊
BMC MEDICAL GENETICS
卷 15, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2350-15-53
关键词
Osteoarthritis; Genetic risk; Single nucleotide polymorphism; Allelic imbalance; Linkage disequilibrium
资金
- Arthritis Research UK
- NIHR Newcastle Biomedical Research Centre
- European Union Seventh Framework Program (D-BOARD) [305815]
- arcOGEN - Arthritis Research UK [18030]
- Medical Research Council [MR/K006312/1] Funding Source: researchfish
- Versus Arthritis [19824] Funding Source: researchfish
- MRC [MR/K006312/1] Funding Source: UKRI
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.
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