英国维康信托桑格研究所（Wellcome Trust Sanger Institute）的研究人员借助基因组相关性扫描（genome-wide association scan）技术，发现了一个骨关节炎发病密切相关的突变基因—MCF2L。相关研究结果于9月9日刊登在《美国人类遗传学杂志》（American Journal of Human Genetics）期刊上。
骨关节炎是一种有着多个遗传学病因的复杂疾病，临床表现为因关节软骨退行性病变引起的关节疼痛和关节畸形。该病的发病率随年龄的增长而增高，尤其在70岁以上的人群中，骨关节炎的发病率高达40%。由于其病因十分复杂，之前仅有两个与疾病发生相关的基因被证实，分别是GDF5基因和位于7号染色体上的一个信号区域基因。
此次，研究人员通过与包括冰岛、爱沙尼亚、荷兰在内的多中心国际合作，总共调查了19041份临床资料。借助基因组相关性扫描技术，研究人员首先将3177份骨关节炎患者与4894份健康人群的基因组数据对比，初筛到600 000个突变基因，再经过一系列的信息核对，确定了1000份资料详尽的基因组项目数据，并从中筛选到了迄今为止第三个与骨关节炎发病相关的遗传学基因突变。新发现的突变基因名为MCF2L，位于第13号染色体，本身编码一种神经生长因子（NGF）。据英国关节炎研究学会（Arthritis Research U）医学部主任Alan Silman介绍，过去，曾有报道显示用抗神经生长因子的抗体治疗骨关节炎患者可以明显减轻患者的疼痛并且改善疾病。随着MCF2L基因突变与骨关节炎发病相关性的揭示，人们开始逐渐意识到神经生长因子的功能异常可能是导致骨关节炎的重要病因。MCF2L基因的编码产物可能在软骨关节行使正常功能时发挥作用，因此，该基因的突变导致了骨关节炎的发病。
下一步，研究人员将深入挖掘这1000份基因组数据，以期更充分地揭示骨关节炎的病因，为研发新的治疗方案提供线索。(生物谷 Bioon.com)
doi:10.1016/j.ajhg.2011.08.001
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A Variant in MCF2L Is Associated with Osteoarthritis
Aaron G. Day-Williams1, Lorraine Southam1, 2, Kalliope Panoutsopoulou1, Nigel W. Rayner2, Tonu Esko3, 4, 5, Karol Estrada6, 7, Hafdis T. Helgadottir8, Albert Hofman9, Throvaldur Ingvarsson10, 11, Helgi Jonsson11, 12, Aime Keis13, 14, Hanneke J.M. Kerkhof6, 7, Gudmar Thorleifsson8, Nigel K. Arden15, 16, Andrew Carr17, Kay Chapman17, Panos Deloukas1, John Loughlin18, Andrew McCaskie18, 19, William E.R. Ollier20, Stuart H. Ralston21, Timothy D. Spector22, Gillian A. Wallis23, J. Mark Wilkinson24, 2
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.111.23], p = 2.1 108) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients. Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.111.23], p = 2.1 108) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.
