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The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis.
Osteoarthritis Cartilage. 2005 Jun; 13(6):497-507.OC

Abstract

OBJECTIVE

We sought to determine whether sequence variations in cartilage collagen genes are associated with primary, early-onset osteoarthritis (OA).

METHODS

The cartilage collagen genes, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1 and COL11A2, were screened for sequence variations in 72 Finnish probands and one US family with primary early-onset hip and/or knee OA. In addition, allelic association studies were performed using six to 12 common polymorphisms from each gene by genotyping 72 OA patients and 103 controls.

RESULTS

Altogether 239 sequence variations were found, of which 16 were not present in the controls. Seven of the unique variations, four in COL11A1, two in COL11A2 and one in COL2A1, were studied further, because they resulted in the substitution of conserved amino acids or were predicted to affect mRNA splicing. Co-segregation of a sequence variation and the phenotype was found in all four families available for study. Association analysis failed to identify any common predisposing alleles.

CONCLUSIONS

Early-onset OA demonstrates locus and allelic heterogeneity since the identified variations were in three different collagen genes and each of the six probands had a different mutation. It is also possible that some OA cases represent the mild end of the chondrodysplasia phenotypic spectrum. The major susceptibility alleles in this form of OA, however, remain to be identified.

Authors+Show Affiliations

Jakkula E
Collagen research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
Melkoniemi M
No affiliation info available
Kiviranta I
No affiliation info available
Lohiniva J
No affiliation info available
Räinä SS
No affiliation info available
Perälä M
No affiliation info available
Warman ML
No affiliation info available
Ahonen K
No affiliation info available
Kröger H
No affiliation info available
Göring HH
No affiliation info available
Ala-Kokko L
No affiliation info available

MeSH

AdultAgedCartilage, ArticularCollagenCollagen Type IICollagen Type IXCollagen Type XIFemaleHumansMaleMiddle AgedMutationOsteoarthritisPedigreePolymerase Chain ReactionPolymorphism, GeneticSequence Analysis, RNA

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15922184

Citation

Jakkula, E, et al. "The Role of Sequence Variations Within the Genes Encoding Collagen II, IX and XI in Non-syndromic, Early-onset Osteoarthritis." Osteoarthritis and Cartilage, vol. 13, no. 6, 2005, pp. 497-507.
Jakkula E, Melkoniemi M, Kiviranta I, et al. The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. Osteoarthritis Cartilage. 2005;13(6):497-507.
Jakkula, E., Melkoniemi, M., Kiviranta, I., Lohiniva, J., Räinä, S. S., Perälä, M., Warman, M. L., Ahonen, K., Kröger, H., Göring, H. H., & Ala-Kokko, L. (2005). The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. Osteoarthritis and Cartilage, 13(6), 497-507.
Jakkula E, et al. The Role of Sequence Variations Within the Genes Encoding Collagen II, IX and XI in Non-syndromic, Early-onset Osteoarthritis. Osteoarthritis Cartilage. 2005;13(6):497-507. PubMed PMID: 15922184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. AU - Jakkula,E, AU - Melkoniemi,M, AU - Kiviranta,I, AU - Lohiniva,J, AU - Räinä,S S, AU - Perälä,M, AU - Warman,M L, AU - Ahonen,K, AU - Kröger,H, AU - Göring,H H H, AU - Ala-Kokko,L, PY - 2004/06/14/received PY - 2005/02/06/accepted PY - 2005/6/1/pubmed PY - 2005/9/30/medline PY - 2005/6/1/entrez SP - 497 EP - 507 JF - Osteoarthritis and cartilage JO - Osteoarthritis Cartilage VL - 13 IS - 6 N2 - OBJECTIVE: We sought to determine whether sequence variations in cartilage collagen genes are associated with primary, early-onset osteoarthritis (OA). METHODS: The cartilage collagen genes, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1 and COL11A2, were screened for sequence variations in 72 Finnish probands and one US family with primary early-onset hip and/or knee OA. In addition, allelic association studies were performed using six to 12 common polymorphisms from each gene by genotyping 72 OA patients and 103 controls. RESULTS: Altogether 239 sequence variations were found, of which 16 were not present in the controls. Seven of the unique variations, four in COL11A1, two in COL11A2 and one in COL2A1, were studied further, because they resulted in the substitution of conserved amino acids or were predicted to affect mRNA splicing. Co-segregation of a sequence variation and the phenotype was found in all four families available for study. Association analysis failed to identify any common predisposing alleles. CONCLUSIONS: Early-onset OA demonstrates locus and allelic heterogeneity since the identified variations were in three different collagen genes and each of the six probands had a different mutation. It is also possible that some OA cases represent the mild end of the chondrodysplasia phenotypic spectrum. The major susceptibility alleles in this form of OA, however, remain to be identified. SN - 1063-4584 UR - https://www.unboundmedicine.com/medline/citation/15922184/The_role_of_sequence_variations_within_the_genes_encoding_collagen_II_IX_and_XI_in_non_syndromic_early_onset_osteoarthritis_ DB - PRIME DP - Unbound Medicine ER -