Dataset Information

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case-control studies.

ABSTRACT: BACKGROUND: Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins ?5?1, ?v?3, and ?v?5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population. METHODS: Two independent case-control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin ?V gene (ITGAV) were detected using the ABI 7500 real-time PCR system. RESULTS: The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR?=?1.44; 95% CI?=?1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population. CONCLUSIONS: Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

SUBMITTER: Yang HY

PROVIDER: S-EPMC4050217 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case-control studies.

Yang Hsin-Yi HY Su Sui-Lung SL Peng Yi-Jen YJ Wang Chih-Chien CC Lee Herng-Sheng HS Salter Donald M DM Lee Chian-Her CH

BMC musculoskeletal disorders 20140523

<h4>Background</h4>Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins α5β1, αvβ3, and αvβ5. The purpos ...[more]

PMID: 24886251

Similar Datasets

Project description:ObjectiveWe aimed to describe the natural history leading to end-stage knee osteoarthritis (esKOA), focusing on knee symptoms, radiographic severity, and the presence of limited mobility or instability.MethodsWe performed knee-based analyses of Osteoarthritis Initiative data from 7691 knees (4165 participants). We used a validated definition of esKOA that relied on meeting one of two criteria: (1) severe radiographic knee osteoarthritis (Kellgren-Lawrence [KL] grade=4) with moderate-to-intense pain (Likert WOMAC pain+function>11/88) or (2) KL grade<4 with intense or severe pain (WOMAC pain+function>22) and limited mobility (flexion contracture≥5°) or instability (based on a varus and valgus stress test). We also introduced an alternate definition of esKOA that relied on meeting one of two criteria that omitted physical exam findings:(1) severe radiographic knee osteoarthritis (KL grade=4) with at least moderate symptoms or (2) KL grade=2 or 3 with intense or severe symptoms and persistent knee pain (frequent knee pain during three or more months in the past year). We used descriptive statistics to explore the frequency of components of esKOA at the index visit when they had incident esKOA, at the annual visit before developing esKOA, and the interval change between those visits.ResultsOur analytic sample was mostly female (58%), without radiographic knee osteoarthritis (KL grade=0 or 1; 60%), without stability or mobility concerns (91%), and without persistent knee pain (77%). At the visit before incident esKOA, most knees already had moderate-to-severe radiographic osteoarthritis using the original (62%) or alternate (50%) definition (versus <15% for either definition of no esKOA). Over 80% of knees that reached the criteria for esKOA achieved this based on increased knee symptom severity - typically without worsening radiographic severity (80%).ConclusionRadiographic severity predisposed a knee to esKOA. However, worsening knee symptoms led to the development of incident esKOA. If investigators want to increase the chance of identifying incident esKOA as an outcome, they should enrich their study samples with people with moderate-to-severe radiographic osteoarthritis. Our findings also highlight the potential reversibility of esKOA (a knee that is classified with esKOA but later is not classified with esKOA). Reversibility is not a flaw of an outcome defining esKOA but rather a desirable clinical outcome to demonstrate a therapeutic intervention can help people with esKOA improve their knee symptoms and delay a knee replacement.

Project description:BackgroundSarcopenia often accompanies osteoarthritis (OA), which is managed by total knee arthroplasty (TKA) in the late stage. Recent studies have suggested a higher risk of post-operative complications after TKA in sarcopenic OA subjects, but whether TKA can benefit them similar to non-sarcopenic subjects remains unexplored. This study aimed to examine the dynamic, mutual impact of sarcopenia and TKA in a one-year post-operative period.MethodsThis prospective cohort study was conducted between 2015 to 2018 at our hospital. Patients with end-stage OA of the knee waiting for TKA were recruited into the study. Primary outcome measures were change in muscle strength, mass and function. Secondary outcome measures were quality of life (QOL) measurements for pain, psychological and physical health.ResultsFifty-eight patients were recruited, of which 79.3% were female and 32.8% already had sarcopenia at baseline. The average age of sarcopenic subjects and non-sarcopenic subjects was comparable (67.89?±?7.07 vs. 67.92?±?6.85; p?=?0.99), but sarcopenic subjects had a lower body mass index (BMI) (25.64?±?2.64 vs. 28.57?±?4.04; p?=?0.01). There was a statistically significant improvement in walking speed (10.24?±?5.35 vs. 7.69?±?2.68, p?<?0.01) and muscle strength in both sarcopenic and non-sarcopenic patients after TKA. This was accompanied by an improvement trend in muscle mass in all subjects. There was no change in handgrip power before and after TKA and subsequent follow-up (19.31?±?5.92 vs. 18.98?±?6.37 vs. 19.36?±?7.66; p?=?0.97). QOL measured before, after and at follow-up with WOMAC (total: 42.27?±?15.98 vs. 20.65?±?15.24 vs. 16.65?±?18.13) and SF12v2 (PCS: 33.06?±?8.55 vs. 38.96?±?8.01 vs. 40.67?±?7.93) revealed progressive significant improvement (both comparisons p???0.01). Further analysis with the IPAQ also found increased engagement of high-intensity activities.ConclusionsThis study showed that sarcopenia among patients with end-stage OA of the knee is not uncommon, but both sarcopenic and non-sarcopenic OA patients achieved significant clinical and functional improvement after TKA. Further studies with a larger sample size and different ethnicities could help ascertain a beneficial role of TKA in sarcopenic OA subjects.Trial registrationRegistry: ClinicalTrials.gov , Registration number: NCT03579329 . Date of registration: 6 July 2018. Retrospectively registered.

Dataset Information

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case-control studies.

Publications

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case-control studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets