Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia

• Published in: Bone & joint research Vol. 6; no. 7; pp. 439 - 445
• Main Authors: Sekimoto, T, Ishii, M, Emi, M, Kurogi, S, Funamoto, T, Yonezawa, Y, Tajima, T, Sakamoto, T, Hamada, H, Chosa, E
• Format: Journal Article
• Language: English
• Published: England British Editorial Society of Bone & Joint Surgery 01.07.2017
• Subjects: Acetabulum; Aspartic acid; Bone dysplasia; Chromosome 9; Copy number; DNA microarrays; Gene polymorphism; Genomes; Hip; Joint surgery; Leukocytes; Oligonucleotides; Osteoarthritis; Osteotomy; Peripheral blood; Statistical analysis; Total hip arthroplasty; ASPN gene; Acetabular dysplasia; Copy number variation
• ISSN: 2046-3758; 2046-3758
• DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin ( ) gene; therefore, the present study aimed to investigate whether the CNV of is involved in the pathogenesis of AD. Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent's region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher's exact probability test, Pearson's correlation test, and Student's -test). CNV analysis of the gene revealed a copy number loss in significantly more AD patients (9/64) than control subjects (0/32; p = 0.0212). This loss occurred within a 60 kb region on 9q22.31, which harbours the gene for . The mean radiological parameters of these AD patients were significantly worse than those of the other subjects (Sharp angle, p = 0.0056; CE angle, p = 0.0076; ARO angle, p = 0.0065), and all nine patients required operative therapy such as total hip arthroplasty or pelvic osteotomy. Moreover, six of these nine patients had a history of operative or conservative therapy for developmental dysplasia of the hip. Copy number loss within the region harbouring the gene on 9q22.31 is associated with severe AD. A copy number loss in the gene region may play a role in the aetiology of severe AD. T. Sekimoto, M. Ishii, M. Emi, S. Kurogi, T. Funamoto, Y. Yonezawa, T. Tajima, T. Sakamoto, H. Hamada, E. Chosa. Copy number loss in the region of the gene in patients with acetabular dysplasia: CNV in acetabular dysplasia. 2017;6:439-445. DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1.