title: Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis.
abstract: Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.
authors.affiliation: SNP Research Center, RIKEN (The Institute of Physical and Chemical Research, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: A
authors.initials: A
authors.lastname: Mabuchi
authors.forename: A
authors.initials: A
authors.lastname: Fukuda
authors.forename: H
authors.initials: H
authors.lastname: Hiraoka
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Machida
authors.forename: Y
authors.initials: Y
authors.lastname: Takatori
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D027321:Anion Transport Proteins; D044466:Asian People; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002358:Cartilage, Articular / Q000503:physiopathology; D017931:DNA Primers; D005091:Exons; D006239:Haplotypes; D006801:Humans; D007438:Introns; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes / Q000235:genetics*; D016017:Odds Ratio; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013430:Sulfate Adenylyltransferase / Q000235:genetics*; D000076988:Sulfate Transporters; D014041:Tokyo
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase