英國維康信托桑格研究所（Wellcome Trust Sanger Institute）的研究人員借助基因組相關性掃描（genome-wide association scan）技術,，發(fā)現(xiàn)了一個骨關節(jié)炎發(fā)病密切相關的突變基因—MCF2L,。相關研究結果于9月9日刊登在《美國人類遺傳學雜志》（American Journal of Human Genetics）期刊上。
骨關節(jié)炎是一種有著多個遺傳學病因的復雜疾病,，臨床表現(xiàn)為因關節(jié)軟骨退行性病變引起的關節(jié)疼痛和關節(jié)畸形。該病的發(fā)病率隨年齡的增長而增高,，尤其在70歲以上的人群中,，骨關節(jié)炎的發(fā)病率高達40%。由于其病因十分復雜,，之前僅有兩個與疾病發(fā)生相關的基因被證實,，分別是GDF5基因和位于7號染色體上的一個信號區(qū)域基因。
此次,，研究人員通過與包括冰島,、愛沙尼亞、荷蘭在內的多中心國際合作,，總共調查了19041份臨床資料,。借助基因組相關性掃描技術，研究人員首先將3177份骨關節(jié)炎患者與4894份健康人群的基因組數(shù)據(jù)對比,，初篩到600 000個突變基因,，再經過一系列的信息核對，確定了1000份資料詳盡的基因組項目數(shù)據(jù),，并從中篩選到了迄今為止第三個與骨關節(jié)炎發(fā)病相關的遺傳學基因突變,。新發(fā)現(xiàn)的突變基因名為MCF2L,，位于第13號染色體，本身編碼一種神經生長因子（NGF）,。據(jù)英國關節(jié)炎研究學會（Arthritis Research U）醫(yī)學部主任Alan Silman介紹,，過去，曾有報道顯示用抗神經生長因子的抗體治療骨關節(jié)炎患者可以明顯減輕患者的疼痛并且改善疾病,。隨著MCF2L基因突變與骨關節(jié)炎發(fā)病相關性的揭示,，人們開始逐漸意識到神經生長因子的功能異常可能是導致骨關節(jié)炎的重要病因,。MCF2L基因的編碼產物可能在軟骨關節(jié)行使正常功能時發(fā)揮作用,，因此，該基因的突變導致了骨關節(jié)炎的發(fā)病,。
下一步,，研究人員將深入挖掘這1000份基因組數(shù)據(jù)，以期更充分地揭示骨關節(jié)炎的病因,，為研發(fā)新的治療方案提供線索,。(生物谷 Bioon.com)
doi:10.1016/j.ajhg.2011.08.001
PMC:
PMID:
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.
