Miyamoto Yoshinari, Mabuchi Akihiko, Shi Dongquan, Kubo Toshikazu, Takatori Yoshio, Saito Susumu, Fujioka Mikihiro, Sudo Akihiro, Uchida Atsumasa, Yamamoto Seizo, Ozaki Koichi, Takigawa Masaharu, Tanaka Toshihiro, Nakamura Yusuke, Jiang Qing, Ikegawa Shiro
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nat Genet. 2007 Apr;39(4):529-33. doi: 10.1038/2005. Epub 2007 Mar 25.
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.
骨关节炎（MIM 165720）以关节软骨退变为特征，是人类关节炎最常见的形式，也是全球老龄化社会的主要关注点。流行病学和遗传学研究表明，骨关节炎是一种多基因疾病。在此，我们报告编码生长分化因子5（GDF5）的基因与亚洲人群的骨关节炎相关。GDF5 5'UTR中的一个单核苷酸多态性（+104T/C；rs143383）在两个独立的日本人群中与髋骨关节炎显示出显著关联（P = 1.8 x 10^(-13)）。这种关联在日本人群的膝骨关节炎（P = 0.0021）和汉族人群（P = 0.00028）中得到了重复验证。这个位于GDF5核心启动子的单核苷酸多态性在软骨形成细胞的转录活性上表现出等位基因差异，易感性等位基因的活性降低。我们的研究结果表明GDF5是骨关节炎的一个易感基因，并提示GDF5表达降低参与了骨关节炎的发病机制。
