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Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.

ABSTRACT: OBJECTIVE:To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. METHODS:We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome-wide association study. We built 3 SSMs capturing the shape variation of the OA-unaffected proximal femur in the entire mixed-sex cohort and for male/female-stratified cohorts. We selected 41 candidate single-nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype-phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. RESULTS:The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P?=?0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed-sex SSM (P?=?0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed-sex SSM (P?=?0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. CONCLUSION:These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape.

SUBMITTER: Lindner C

PROVIDER: S-EPMC4864451 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.

Lindner Claudia C Thiagarajah Shankar S Wilkinson J Mark JM Panoutsopoulou Kalliope K Day-Williams Aaron G AG Cootes Timothy F TF Wallis Gillian A GA

Arthritis & rheumatology (Hoboken, N.J.) 20150501 8

<h4>Objective</h4>To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits.<h4>Methods</h4>We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome-wide association study. We buil ...[more]

PMID: 25939412

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Project description:Study questionIs there concordance between hip pain and radiographic hip osteoarthritis?MethodsIn this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test.Study answer and limitationsIn the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations.What this study addsHip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs.Funding, competing interests, data sharingSee the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu.

Project description:INTRODUCTION: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals. METHODS: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis. RESULTS: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features. CONCLUSIONS: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.

Project description:BackgroundTotal hip arthroplasty (THA) is the treatment of choice for posttraumatic arthritis with failed internal fixation for hip fractures. However, the postoperative prognosis is not clear.Questions/purposesThe primary aim of the study is to report the postoperative outcome, prognosis, and complication rates of total hip arthroplasty in posttraumatic hip arthritis after failed internal fixation of fractures around the hip. The secondary aim of the study is to report results among different fracture types around the hip.Patients and methodsWe enrolled salvage THA patients after failed internal fixation of fractures around the hip and matched control patients undergoing primary THA for hip osteoarthritis. Subgroup analysis was performed to compare the postoperative outcomes, prognosis, and complication rates of salvage THA in posttraumatic hip arthritis after failed internal fixation of different fracture types around the hip.ResultsA total of 315 THAs (105 salvage THAs and 210 primary THAs) were analyzed. Patients with salvage THA had a longer operative time, lower postoperative hemoglobin (Hb) level, more Hb drop (2.2 ± 1.4 vs. 1.7 ± 1.2 gm/dl, p = 0.002), and delayed ambulation. The salvage THA group also had a higher dislocation rate within 2 months after salvage THA (9.5% vs. 1.9%, p = 0.002), reoperation rate (10.5% vs. 3.8%, p = 0.019, including debridement, open and closed reduction under sedation, revision surgery, surgical fixation for periprosthetic fractures), and revision rate (5.7% vs. 0.5%, p = 0.003) than patients undergoing primary THA. Patients who had failed fixation for acetabular fractures were younger and tended to recover well. Patients with previous intertrochanteric fracture had the longest operative time, more hip pain (83.8%, p = 0.022) and more complications.ConclusionSalvage THA in posttraumatic hip arthritis after failed internal fixation required a longer operative time and led to more blood loss and postoperative complications. The dislocation, reoperation, and revision rates after salvage THA were higher than those after primary THA. Patients with salvage THA after failed internal fixation for intertrochanteric fractures were the most susceptible to more complications compared to those with femoral neck fracture or acetabular fracture. Level of Evidence level III.

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Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.

Publications

Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.

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