Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVES: To determine by genetic association analysis whether the 4q functional candidate genes IGFBP7, ADAMTS3, and IL8 might encode for susceptibility to osteoarthritis (OA). METHODS: Expression of IGFBP7, ADAMTS3, and IL8 in adult OA articular cartilage chondrocytes was demonstrated by reverse transcription-polymerase chain reaction. The genes were screened for common polymorphic DNA variants by direct sequencing of exons, intron-exon boundaries, and the 5' and 3' untranslated regions. The variants were genotyped in the female probands from the 146 families which each contained two or more sisters who had undergone total hip replacement (THR) and in 375 female controls matched for age. Variants showing evidence for association were subsequently genotyped in 244 female-THR patients with OA. Allele frequencies between the probands (or patients) and the controls were compared by chi(2) analysis. RESULTS: Fourteen common variants were identified in the three genes. An ADAMTS3 single nucleotide polymorphism was associated in the probands (p = 0.015) and an ADAMTS3 insertion/deletion approached significance (p = 0.059). However, neither variant was associated in the additional 244 patients with hip OA, with p values of 0.12 and 0.19, respectively. CONCLUSIONS: The analysis implies that the chromosome 4q female hip OA susceptibility is not coded for by polymorphism within the functional candidates IGFBP7, ADAMTS3, or IL8.

Original publication




Journal article


Ann Rheum Dis

Publication Date





474 - 476


ADAM Proteins, ADAMTS Proteins, Aged, Cartilage, Articular, Chondrocytes, Chromosomes, Human, Pair 4, Endopeptidases, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Insulin-Like Growth Factor Binding Proteins, Interleukin-8, Middle Aged, Osteoarthritis, Hip, Procollagen N-Endopeptidase