The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis
The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis
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DOI：
10.1016/j.joca.2005.02.005
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发表时间：
2005-06-01
影响因子：
7
通讯作者：
Ala-Kokko, L
中科院分区：
文献类型：
--
作者：
Jakkula, E;Melkoniemi, M;Ala-Kokko, L
目的：我们试图确定软骨胶原基因的序列变异是否与原发性早发性骨关节炎（OA）相关。方法：对72例芬兰先证和1例美国原发性早发性髋关节和/或膝关节OA家族的软骨胶原基因COL2A1、COL9A1、COL9A2、COL9A3、COL11A1和COL11A2进行序列变异筛选。此外，通过对72例OA患者和103例对照进行基因分型，对每个基因的6 - 12个常见多态性进行等位基因关联研究。结果：共发现239个序列变异，其中16个在对照组中不存在。7个独特的变异，4个在COL11A1中，2个在COL11A2中，1个在COL2A1中，被进一步研究，因为它们导致了保守氨基酸的替代，或者被预测会影响mRNA剪接。在所有四个可研究的家族中均发现了序列变异和表型的共分离。关联分析未发现任何共同的易感等位基因。结论：早发性OA表现出位点和等位基因的异质性，因为所鉴定的变异存在于三种不同的胶原基因中，并且六个先证者中的每一个都有不同的突变。也有可能一些OA病例代表软骨发育不良表型谱的轻度末端。然而，这种形式OA的主要易感等位基因仍有待确定。(C) 2005国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: We sought to determine whether sequence variations in cartilage collagen genes are associated with primary, early-onset osteoarthritis (OA).Methods: The cartilage collagen genes, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1 and COL11A2, were screened for sequence variations in 72 Finnish probands and one US family with primary early-onset hip and/or knee OA. In addition, allelic association studies were performed using six to 12 common polymorphisms from each gene by genotyping 72 OA patients and 103 controls.Results: Altogether 239 sequence variations were found, of which 16 were not present in the controls. Seven of the unique variations, four in COL11A1, two in COL11A2 and one in COL2A1, were studied further, because they resulted in the substitution of conserved amino acids or were predicted to affect mRNA splicing. Co-segregation of a sequence variation and the phenotype was found in all four families available for study. Association analysis failed to identify any common predisposing alleles.Conclusions: Early-onset OA demonstrates locus and allelic heterogeneity since the identified variations were in three different collagen genes and each of the six probands had a different mutation. It is also possible that some OA cases represent the mild end of the chondrodysplasia phenotypic spectrum. The major susceptibility alleles in this form of OA, however, remain to be identified. (C) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.