Kim Clipsham

Osteoarthritis-Susceptibility Locus on Chromosome 11q, Detected by Linkage

We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P</=.05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers on chromosome 11q. Additional markers from this region were then typed to create a denser map. We obtained a maximum single-point LOD score, at D11S901, of 2.40 (P=.0004) and a maximum multipoint-LOD score of 3.15, between markers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P=.0003) for marker D11S901, with evidence for linkage extending 12 cM proximal to this marker. When we stratified for affected male sibling pairs there was no evidence of linkage to chromosome 11. Our data suggest that a female-specific susceptibility gene for idiopathic osteoarthritis is located on chromosome 11q.

Genetic influences in the aetiology of tears of the rotator cuff: SIBLING RISK OF A FULL-THICKNESS TEAR

From a retrospective, cohort study of 205 patients diagnosed with full-thickness tears of the rotator cuff, we determined, using ultrasound, the prevalence of such tears in their 129 siblings. Using 150 spouses as controls, the relative risk of full-thickness tears in siblings versus controls was 2.42 (95% CI 1.77 to 3.31). The relative risk of symptomatic full-thickness tears in siblings versus controls was 4.65 (95% CI 2.42 to 8.63). The significantly increased risk for tears in siblings implies that genetic factors play a major role in the development of full-thickness tears of the rotator cuff.

GENETIC INFLUENCES IN END-STAGE OSTEOARTHRITIS

From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95 % CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%. The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Genetic background increases the risk of hip osteoarthritis.

Using a cohort of 49 families with at least one affected female sibling pair who had total hip arthroplasty for end-stage primary osteoarthritis, we determined the prevalence and relative risk of symptomatic and radiographic osteoarthritis in 145 children. The relative risk of symptomatic radiographic osteoarthritis in these 145 offspring was 3.5 times greater than in 119 age-matched controls (95% confidence interval; range, 2.0–6.2). Most symptoms and radiographic changes involved the hip. Results of this study showed vertical transmission of primary osteoarthritis and that genetic influences play a major role in osteoarthritis of the hip in the Caucasian population. Level of Evidence: Prognostic study, Level II-1 (prospective cohort study)