Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues
Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues
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DOI：
10.1136/annrheumdis-2011-200981
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发表时间：
2012-07-01
影响因子：
27.4
通讯作者：
Meulenbelt, Ingrid
中科院分区：
文献类型：
--
作者：
Bos, Steffan D.;Bovee, Judith V. M. G.;Meulenbelt, Ingrid
目的II型脱碘酶（D2）基因（DIO2）的遗传变异是骨关节炎（OA）的危险因素。为了研究这种关联的可能机制，我们评估了健康软骨和OA影响软骨中的D2蛋白，并研究了OA风险多态性rs225014在人类OA关节中DIO2的等位基因平衡。方法对D2正常软骨和oa影响软骨进行免疫组化染色。然后，我们评估了在病变、韧带和软骨下骨附近和附近受oa影响的软骨中DIO2 mRNA的等位基因平衡。等位基因平衡通过杂合携带者基因内OA风险多态性rs225014的等位基因“C”和“T”数量来衡量。结果OA软骨中D2阳性细胞数量和染色强度明显增高。与DIO2的“T”等位基因相比，oa相关的rs225014“C”等位基因的存在率显著高出1.3倍，在31名供者中有28人具有显著性。结论OA软骨中D2蛋白含量升高。在杂合子携带者中，rs225014的OA风险等位基因“C”比“C”型“T”等位基因更丰富，这种DIO2 mRNA转录物的等位基因失衡可能是DIO2遗传变异导致OA风险的一种机制。
Objective Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage and investigated allelic balance of the OA risk polymorphism rs225014 at DIO2 in human OA joints.Methods Immunohistochemical staining of healthy and OA-affected cartilage was performed for D2. We then assessed allelic balance of DIO2 mRNA within OA-affected cartilage both at and away from the lesion, ligaments and subchondral bone. Allelic balance was measured by the amount of alleles 'C' and 'T' of the intragenic OA risk polymorphism rs225014 in heterozygous carriers.Results A markedly higher amount of D2 positive cells and staining intensity was observed in OA cartilage. A significant, 1.3-fold higher presence was observed for the OA-associated rs225014 'C' allele relative to the 'T' allele of DIO2, which was significant in 28 of 31 donors.Conclusion In OA cartilage, D2 protein presence is increased. The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele 'C' of rs225014 more abundant than the 'C' type 'T' allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.