Variations in three genes related to collagen and bone formation have been linked to developmental dysplasia of the hip (DDH) and hip osteoarthritis, according to findings released on Apr. 17 by a multinational research team. The study, led by Dr. Ryosuke Yamaguchi from Kyushu University and Dr. Chikashi Terao of the RIKEN Center for Integrative Medical Sciences, analyzed genetic data from tissue samples in Japan, the United Kingdom, and across Europe.
DDH is an abnormality of the hip joint that can lead to issues with posture and movement as early as infancy. Individuals with DDH are at increased risk for developing osteoarthritis due to abnormal wear on the joint. Family history is a significant factor; people with a parent or sibling affected by DDH are twelve times more likely to develop the disorder themselves.
The researchers conducted genome-wide association studies (GWAS) focusing on genetic variations shared between DDH and hip osteoarthritis but not present in healthy individuals. Their meta-analysis included approximately 350,000 samples from Europe, making it one of the largest GWAS efforts targeting these conditions so far.
They found that three gene loci—COL11A2 (involved in collagen production), CALN1 (encoding a calcium-binding protein), and TRPM7 (regulating magnesium and calcium ion levels)—were common factors for both DDH and hip osteoarthritis. COL11A2 and CALN1 appeared to influence different aspects of DDH subtypes such as hip dysplasia without dislocation versus those with dislocation. "In total, nine loci were identified for DDH and its subtypes, with hip dysplasia without dislocation showing distinct genetic signals from hip dislocation," said Dr. Yamaguchi. He added: "Taken together, these suggest that while polygenic architecture is largely shared between the two subsets of DDH, there are genetic differences in a part of specific genetic loci."
Further analysis revealed that genes involved in bone cell growth also play roles in both disorders' progression; non-coding DNA regions may regulate functional genes similarly across both diseases.
"This study identified susceptibility loci to DDH and hip OA and candidates of responsible genes in the loci," said Dr. Terao. He continued: "These findings underscore the need for future DDH-specific multi-omics studies, integrating genetic data with tissue-specific gene expression, chromatin accessibility, and spatial chromatin structure, especially in chondrocytes, to fully elucidate the functional mechanisms underlying this complex disorder."
The researchers say their work could help pave the way toward more targeted therapies aimed at slowing disease progression or improving quality of life for those affected.
