Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q.
OBJECTIVE
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.
Kawahara
C
C
University of Oxford, Institute of Musculoskeletal Science, Botnar Research Centre, Oxford OX3 7LD, UK.
Forster
T
T
Chapman
K
K
Carr
A
A
Loughlin
J
J
D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000235:genetics*; D011348:Procollagen N-Endopeptidase
D018969:Insulin-Like Growth Factor Binding Proteins; D016209:Interleukin-8; C102529:insulin-like growth factor binding protein-related protein 1; D010450:Endopeptidases; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C434951:ADAMTS3 protein, human; D011348:Procollagen N-Endopeptidase