title: A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis.
abstract: Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.
authors: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors: Yoshinari
authors: Y
authors: Miyamoto
authors: Akihiko
authors: A
authors: Mabuchi
authors: Dongquan
authors: D
authors: Shi
authors: Toshikazu
authors: T
authors: Kubo
authors: Yoshio
authors: Y
authors: Takatori
authors: Susumu
authors: S
authors: Saito
authors: Mikihiro
authors: M
authors: Fujioka
authors: Akihiro
authors: A
authors: Sudo
authors: Atsumasa
authors: A
authors: Uchida
authors: Seizo
authors: S
authors: Yamamoto
authors: Koichi
authors: K
authors: Ozaki
authors: Masaharu
authors: M
authors: Takigawa
authors: Toshihiro
authors: T
authors: Tanaka
authors: Yusuke
authors: Y
authors: Nakamura
authors: Qing
authors: Q
authors: Jiang
authors: Shiro
authors: S
authors: Ikegawa
mesh_terms: D020121:5' Untranslated Regions; D044466:Asian People / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055428:Growth Differentiation Factor 5; D006801:Humans; D015810:Linkage Disequilibrium; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5