RGD Reference Report - Association study of candidate genes for the prevalence and progression of knee osteoarthritis. - Rat Genome Database

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Association study of candidate genes for the prevalence and progression of knee osteoarthritis.

Authors: Valdes, AM  Hart, DJ  Jones, KA  Surdulescu, G  Swarbrick, P  Doyle, DV  Schafer, AJ  Spector, TD 
Citation: Valdes AM, etal., Arthritis Rheum. 2004 Aug;50(8):2497-507.
RGD ID: 1625347
Pubmed: PMID:15334463   (View Abstract at PubMed)
DOI: DOI:10.1002/art.20443   (Journal Full-text)

OBJECTIVE: Osteoarthritis (OA), characterized by late-onset degeneration of articular cartilage, is recognized to have a genetic component. We examined the role of 26 single-nucleotide polymorphisms (SNPs) from 24 candidate genes in OA susceptibility and progression. METHODS: We compared human complementary DNA libraries from OA-affected and normal cartilage and synovium and selected 22 genes in addition to the estrogen receptor alpha and vitamin D receptor genes. Based on the availability of polymorphisms, we proceeded to test whether genetic variation at those genes affected susceptibility to or progression of radiographic knee OA over a 10-year period in 749 women (mean age 64 years) from the longitudinal Chingford Study. RESULTS: After adjusting for age and body mass index, we observed significant associations at ADAM12, BMP2, CD36, COX2, and NCOR2 with 3 OA susceptibility traits (presence/absence of joint space narrowing [JSN], presence/absence of osteophytes, and Kellgren/Lawrence [K/L] score). For the OA progression traits (change over 10 years in the K/L score, osteophyte grade, and JSN grade), we found significant associations with ADAM12, CILP, OPG, and TNA. Overall, we observed 15 associations with nominal significance (P < 0.05) and, by permutation analysis, found that such a number would be observed by chance only 3.8% of the time. Although these tests require replication, the stronger genetic associations observed are unlikely to be attributable simply to multiple comparisons. CONCLUSION: Our results suggest that OA severity and progression have a multigenic and feature-specific nature. These findings should encourage the development of genetic diagnostics for OA progression based on multiple SNPs and help unravel some of the complex disease mechanisms in OA.



1 to 20 of 24 rows

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
ADAM12Humanosteoarthritis susceptibilityIAGP  RGD 
Adam12Mouseosteoarthritis susceptibilityISOADAM12 (Homo sapiens) RGD 
Adam12Ratosteoarthritis susceptibilityISOADAM12 (Homo sapiens) RGD 
BMP2Humanosteoarthritis susceptibilityIAGP  RGD 
Bmp2Ratosteoarthritis susceptibilityISOBMP2 (Homo sapiens) RGD 
Bmp2Mouseosteoarthritis susceptibilityISOBMP2 (Homo sapiens) RGD 
CD36Humanosteoarthritis susceptibilityIAGP  RGD 
CILPHumanosteoarthritis disease_progressionIAGP  RGD 
CLEC3BHumanosteoarthritis disease_progressionIAGP  RGD 
Cd36Ratosteoarthritis susceptibilityISOCD36 (Homo sapiens) RGD 
Cd36Mouseosteoarthritis susceptibilityISOCD36 (Homo sapiens) RGD 
CilpRatosteoarthritis disease_progressionISOCILP (Homo sapiens) RGD 
CilpMouseosteoarthritis disease_progressionISOCILP (Homo sapiens) RGD 
Clec3bRatosteoarthritis disease_progressionISOCLEC3B (Homo sapiens) RGD 
Clec3bMouseosteoarthritis disease_progressionISOCLEC3B (Homo sapiens) RGD 
NCOR2Humanosteoarthritis susceptibilityIAGP  RGD 
Ncor2Ratosteoarthritis susceptibilityISONCOR2 (Homo sapiens) RGD 
Ncor2Mouseosteoarthritis susceptibilityISONCOR2 (Homo sapiens) RGD 
PTGS2Humanosteoarthritis susceptibilityIAGP DNA:SNP (human)RGD 
Ptgs2Ratosteoarthritis susceptibilityISOPTGS2 (Homo sapiens)DNA:SNP (human)RGD 
1 to 20 of 24 rows


Genes (Rattus norvegicus)
Adam12  (ADAM metallopeptidase domain 12) Bmp2  (bone morphogenetic protein 2) Cd36  (CD36 molecule)
Cilp  (cartilage intermediate layer protein) Clec3b  (C-type lectin domain family 3, member B) Ncor2  (nuclear receptor co-repressor 2)
Ptgs2  (prostaglandin-endoperoxide synthase 2) Tnfrsf11b  (TNF receptor superfamily member 11B)

Genes (Mus musculus)
Adam12  (ADAM metallopeptidase domain 12) Bmp2  (bone morphogenetic protein 2) Cd36  (CD36 molecule)
Cilp  (cartilage intermediate layer protein, nucleotide pyrophosphohydrolase) Clec3b  (C-type lectin domain family 3, member b) Ncor2  (nuclear receptor co-repressor 2)
Ptgs2  (prostaglandin-endoperoxide synthase 2) Tnfrsf11b  (tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin))

Genes (Homo sapiens)
ADAM12  (ADAM metallopeptidase domain 12) BMP2  (bone morphogenetic protein 2) CD36  (CD36 molecule (CD36 blood group))
CILP  (cartilage intermediate layer protein) CLEC3B  (C-type lectin domain family 3 member B) NCOR2  (nuclear receptor corepressor 2)
PTGS2  (prostaglandin-endoperoxide synthase 2) TNFRSF11B  (TNF receptor superfamily member 11b)

Gene Brca1 BRCA1, DNA repair associated Rattus norvegicus