A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease.

ABSTRACT: Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value?=?9.25?×?10(-9)) with the KBD. Replication study observed significant association signal at rs1278300 (p-value?=?0.007) and rs1710287 (p-value?=?0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate?=?47.59?±?7.79%) compared to healthy articular cartilage (average positive chondrocyte rate?=?64.73?±?5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD.

SUBMITTER: Hao J 

PROVIDER: S-EPMC4992896 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature