title: Identification of sequence polymorphisms in CALM2 and analysis of association with hip osteoarthritis in a Japanese population.
abstract: Osteoarthritis (OA) is a degenerative disease characterized by gradual loss of articular cartilage and is a leading cause of disability in elderly populations. In a previous study, we demonstrated an association between a functional single nucleotide polymorphism (SNP) in the core promoter region of the calmodulin (CaM) 1 gene (CALM1) and hip OA. CaM plays an important role in maintaining cartilage phenotype. Three genes, CALM1, CALM2, and CALM3, encode completely identical CaM proteins. In the present study, we investigated the susceptibility of these three genes for hip OA. Expression analyses revealed that CALM2 was most abundantly expressed in articular chondrocytes and OA cartilage. We then identified sequence polymorphisms in the CALM2 region and analyzed their associations with hip OA in a Japanese population. None of the polymorphisms was significantly associated with hip OA, but when the population was stratified according to acetabular dysplasia status, two SNPs located in intron 1 were found to be significantly associated in a subpopulation of the hip OA patients without acetabular dysplasia (P = 0.036 and 0.031, respectively). These findings suggest that the CALM2 gene may be a genetic determinant of hip OA.
authors.affiliation: Pharmacology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85 Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. Mototani_Hideyuki@takeda.co.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mototani
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics* / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: C488659:CALM2 protein, human; D002147:Calmodulin; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human