Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1
Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1
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DOI：
10.1186/1471-2350-15-53
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发表时间：
2014-05-04
影响因子：
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通讯作者：
Loughlin, John
中科院分区：
文献类型：
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作者：
Gee, Fiona;Clubbs, Clare F.;Loughlin, John
背景：骨关节炎 (OA) 易感位点已被定位到染色体 3p21，即包含 12 个基因的高度连锁不平衡区域。其中六个基因在关节组织中表达，因此我们评估了这六个基因中的任何一个是否受到这些组织中活跃的顺式作用调节多态性的影响，从而可以解释关联信号。方法：我们使用焦磷酸测序测定法测量等位基因表达，焦磷酸测序测定法可以区分转录本单核苷酸多态性的每个等位基因的mRNA输出。我们评估了从接受选择性关节置换手术的 OA 患者的软骨和其他关节组织中提取的 RNA。使用双尾曼-惠特尼精确检验来测试任何等位基因差异的显着性。结果：GNL3 和 SPCS1 在 OA 软骨中表现出显着的等位基因表达失衡 (AEI)（GNL3，平均 AEI = 1.04，p = 0.0002；SPCS1，平均 AEI = 1.07，p < 0.0001）。在其他组织中也观察到类似的结果。两个基因的OA相关等位基因的表达均低于非相关等位基因。结论：作用于GNL3和SPCS1的顺式作用调控多态性有助于染色体3p21处的OA关联信号，因此这些基因值得进一步研究。
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.