...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females.
【24h】

Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females.

机译：分泌的卷曲相关蛋白3基因内的功能变异与女性髋骨关节炎有关。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Osteoarthritis (OA) is a leading cause of disability in Western society with multiple risk factors, including a complex genetic pattern. Identifying loci involved in the heredity of OA might lead to insights into the molecular pathogenesis of this common disorder. A previous genome scan mapped a primary hip OA susceptibility locus to chromosome 2q with a maximum multipoint logarithm of odds score of 1.6 in 378 affected sibling pair families. Here, microsatellite targeting of eight candidate genes in this region from 2q23-2q32 demonstrated significant associations with the tumor necrosis factor alpha-induced protein 6 gene in all probands and the integrin alpha 6 and frizzled motif associated with bone development (FRZB) genes in female probands. However, genotyping showed lack of association for a nonsynonymous single-nucleotide polymorphism in tumor necrosis factor alpha-induced protein 6, whereas a single-nucleotide polymorphism in FRZB resulting in an Arg324Gly substitution at the carboxyl terminus was associated with hip OA in the female probands (P = 0.04). This association was confirmed in an independent cohort of female hip cases (n = 338; P = 0.04). In addition, a haplotype coding for substitutions of two highly conserved arginine residues (Arg200Trp and Arg324Gly) in FRZB was a strong risk factor for primary hip OA, with an odds ratio of 4.1 (P = 0.004). FRZB encodes secreted frizzled-related protein 3, which is a soluble antagonist of wingless (wnt) signaling. Variant secreted frizzled-related protein 3 with the Arg324Gly substitution had diminished ability to antagonize wnt signaling in vitro. Hence, functional polymorphisms within FRZB confer susceptibility for hip OA in females and implicate the wnt signaling pathway in the pathogenesis of this disease.
机译：骨关节炎（OA）是西方社会致残的主要原因，它具有多种风险因素，包括复杂的遗传模式。鉴定与OA遗传有关的基因座可能会导致对该常见疾病的分子发病机理的深入了解。先前的基因组扫描在378个受影响的同胞对家庭中将主要髋骨OA易感性基因座映射到2q染色体，最大多点对数比值为1.6。在这里，从2q23-2q32对该区域的八个候选基因的微卫星靶向显示与所有先证者中的肿瘤坏死因子α诱导的蛋白6基因以及女性中的整联蛋白α6和与骨骼发育（FRZB）基因相关的卷曲基序显着相关先证者。然而，基因分型显示肿瘤坏死因子α诱导的蛋白6的非同义单核苷酸多态性缺乏关联，而FRZB中导致羧基末端Arg324Gly取代的单核苷酸多态性与女性先证者的髋骨关节炎相关（P ＝ 0.04）。这种关联在一个独立的女性髋关节病例队列中得到证实（n = 338； P = 0.04）。另外，编码FRZB中两个高度保守的精氨酸残基（Arg200Trp和Arg324Gly）的取代的单倍型是原发性髋关节炎OA的重要危险因素，比值比为4.1（P = 0.004）。 FRZB编码分泌的卷曲相关蛋白3，它是无翅（wnt）信号传导的可溶性拮抗剂。带有Arg324Gly取代的变体分泌的卷曲相关蛋白3在体外拮抗wnt信号的能力减弱。因此，FRZB内的功能多态性赋予女性髋骨OA敏感性，并暗示该疾病的发病机制中的wnt信号通路。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号