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Conference Paper: Three genes in the aggrecan degradation pathway act synergistically to predispose to degenerative disc disease

TitleThree genes in the aggrecan degradation pathway act synergistically to predispose to degenerative disc disease
Authors
Issue Date2007
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://abstracts.spinejournal.com
Citation
The 34th Annual Meeting of International Society for the Study of the Lumbar Spine (ISSLS), Hong Kong, 10-14 June 2007. In Spine-Affiliated Society Meeting Abstracts, 2007, v. 2007, p. 11 How to Cite?
AbstractIntroduction. Degenerative disc disease (DDD) is a multifactorial disorder with genetic predisposition. Aggrecan (AGC1) is the major proteoglycan in the extracellular matrix of the intervertebral disc and is responsible for maintaining disc hydration. Impairment in the structural property of aggrecan through enzymatic degradation could contribute to DDD. Method. Using a previously established Southern Chinese population dataset of 804 individuals with MRI and DNA information, we performed a case-association study for the genes in the aggrecan degradation pathway, including MMP cluster, AGC1, ADAMTS-4,-5 and IL-1 cluster. SNP tags of these candidate genes were selected from HapMap and ABI SNPbrower databases. Polymorphisms were assayed by Sequenom method. Data analysis was carried out using Chi-square, HWE and Fisher’s exact tests. Interaction was analyzed by the set association approach and the combination methods. Result. 15 SNPs were selected from the original 65 SNPs by set association, three of which were detected to be very highly significant associated with IVD when all the three risk factors co-exist [p 0.00001, OR 2.11(1.51–2.95)]. The frequencies of all the three risk factors are 0.32 in controls and 0.50 in cases. Discussion. This is the first genetic study of any kind that demonstrates a combination of genetic predisposing factors within the same pathway are needed to predispose to disease. This has significant implications for the future study of DDD as well as other diseases, as genetic interactions will need to be specifically identified and examined. The combination of genes make good functional sense as they are all involved in the degradation pathway of aggrecan. Future work would need to demonstrate concentrate on how these changes result in DDD.
Persistent Identifierhttp://hdl.handle.net/10722/96505
ISSN

 

DC FieldValueLanguage
dc.contributor.authorCheung, KMCen_HK
dc.contributor.authorSong, YQen_HK
dc.contributor.authorKao, PYPen_HK
dc.contributor.authorHo, DWHen_HK
dc.contributor.authorFan, Ben_HK
dc.contributor.authorKarppinen, Jen_HK
dc.contributor.authorYip, SPen_HK
dc.contributor.authorLeong, JCYen_HK
dc.contributor.authorLuk, KDKen_HK
dc.contributor.authorOtt, Jen_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorChan, D-
dc.date.accessioned2010-09-25T16:35:54Z-
dc.date.available2010-09-25T16:35:54Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 34th Annual Meeting of International Society for the Study of the Lumbar Spine (ISSLS), Hong Kong, 10-14 June 2007. In Spine-Affiliated Society Meeting Abstracts, 2007, v. 2007, p. 11-
dc.identifier.issn1548-2545-
dc.identifier.urihttp://hdl.handle.net/10722/96505-
dc.description.abstractIntroduction. Degenerative disc disease (DDD) is a multifactorial disorder with genetic predisposition. Aggrecan (AGC1) is the major proteoglycan in the extracellular matrix of the intervertebral disc and is responsible for maintaining disc hydration. Impairment in the structural property of aggrecan through enzymatic degradation could contribute to DDD. Method. Using a previously established Southern Chinese population dataset of 804 individuals with MRI and DNA information, we performed a case-association study for the genes in the aggrecan degradation pathway, including MMP cluster, AGC1, ADAMTS-4,-5 and IL-1 cluster. SNP tags of these candidate genes were selected from HapMap and ABI SNPbrower databases. Polymorphisms were assayed by Sequenom method. Data analysis was carried out using Chi-square, HWE and Fisher’s exact tests. Interaction was analyzed by the set association approach and the combination methods. Result. 15 SNPs were selected from the original 65 SNPs by set association, three of which were detected to be very highly significant associated with IVD when all the three risk factors co-exist [p 0.00001, OR 2.11(1.51–2.95)]. The frequencies of all the three risk factors are 0.32 in controls and 0.50 in cases. Discussion. This is the first genetic study of any kind that demonstrates a combination of genetic predisposing factors within the same pathway are needed to predispose to disease. This has significant implications for the future study of DDD as well as other diseases, as genetic interactions will need to be specifically identified and examined. The combination of genes make good functional sense as they are all involved in the degradation pathway of aggrecan. Future work would need to demonstrate concentrate on how these changes result in DDD.-
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://abstracts.spinejournal.com-
dc.relation.ispartofSpine-Affiliated Society Meeting Abstractsen_HK
dc.titleThree genes in the aggrecan degradation pathway act synergistically to predispose to degenerative disc diseaseen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailCheung, KMC: cheungmc@hku.hken_HK
dc.identifier.emailSong, YQ: songy@hkucc.hku.hken_HK
dc.identifier.emailKao, PYP: h0102925@graduate.hku.hken_HK
dc.identifier.emailHo, DWH: waihungh@graduate.hku.hken_HK
dc.identifier.emailFan, B: baojianfan@yahoo.comen_HK
dc.identifier.emailLeong, JCY: hrmolcy@hkucc.hku.hken_HK
dc.identifier.emailLuk, KDK: hrmoldk@hkucc.hku.hken_HK
dc.identifier.emailCheah, KSE: hrmbdkc@hkusua.hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailChan, D: chand@hkucc.hku.hk, chand@hkusua.hku.hken_HK
dc.identifier.authorityCheung, KMC=rp00387en_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.identifier.authorityLuk, KDK=rp00333en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityChan, D=rp00540en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/01.brs.0000317506.98035.21-
dc.identifier.hkuros129413-
dc.identifier.issueMeeting Abstracts p.1-51-
dc.identifier.spage11-
dc.identifier.epage11-
dc.publisher.placeUnited States-

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