Dataset Information

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study.

ABSTRACT:

Introduction

We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.

Methods

OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls.

Results

Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10-4 to 4.1 x10-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with those previously reported for hip OA.

Conclusions

We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joints. This result also shows the interest of analysing other multiallelic polymorphisms.

SUBMITTER: Rodriguez-Fontenla C

PROVIDER: S-EPMC3674626 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Publications

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study.

Rodriguez-Fontenla Cristina C Carr Andrew A Gomez-Reino Juan J JJ Tsezou Aspasia A Loughlin John J Gonzalez Antonio A

Arthritis research & therapy 20121127 6

<h4>Introduction</h4>We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.<h4>Methods</h4>OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or ...[more]

PMID: 23186552

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Project description:IntroductionThe role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several candidate genes have been identified to be associated with it. Among these genes are Bone Morphogenetic Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Transforming Growth Factor (TGF) signaling pathway. The knee is the commonly affected joint, and knee OA has an especially high prevalence in Asian population.AimTo investigate associations between Single Nucleotide Polymorphisms (SNPs) rs12901499 in SMAD3 and rs921126 in the BMP5 gene with knee OA susceptibility in and around Lucknow, Uttar Pradesh, India.Materials and methodsSNPs rs12901499 in SMAD3 and rs921126 in BMP5 were genotyped in patients with knee OA and age- sex matched OA-free controls from our population. A total of 450 patients with knee OA and 458 controls were enrolled in the study. Venous blood samples were obtained from all cases as well as controls for PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Data was collected and entered in excel sheets. Statistical analyses of the data were performed using statistical software package SPSS version 16.0. Chi-square, Student's t-test and logistic regression tests were used to analyse the data.ResultsGA and GG genotypes of both SNPs (rs12901499 and rs921126), and variant G, were associated with a significantly increased risk of knee OA. A significantly increased risk of knee OA was associated with the genotype GG and GA of rs12901499 (p < 0.03 and p <0.004 respectively) and rs921126 (p< 0.0001 and p<0.001 respectively) compared with the AA genotype. In addition, those bearing at least one G allele (GG + GA) had a significantly increased risk of knee OA compared with those without the G allele (AA) in rs921126 (p< 0.0001). However, in rs12901499, significant association with the risk of knee OA was not found (p<0.4). On age and gender based stratification, the association between the risk of OA and rs921126 GG mutant compared with AA homozygotes was strong in both gender (adjusted OR= 2.93 for male and 2.25 for female) and in those aged >55 years (adjusted OR= 3.4), similarly in rs12901499, GG mutant compared with AA homozygote was strong in female (adjusted OR= 1.5) and in those aged >55 years (adjusted OR= 1.5).ConclusionThe results showed that both in SMAD3 rs12901499 and BMP5 921126, G allele is significantly associated with knee OA. A to G change and variant G genotype may contribute to knee OA risk in our study population of Lucknow.

Project description:ObjectivesThe aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case-control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA.MethodsCases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren-Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses.ResultsWorsening of WOMAC scores (cOR 1.02-1.20, p ⩽ 0.012), KOOS (1.02-1.04, p ⩽ 0.014), knee injuries sustained in the previous 30-40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure.ConclusionThis study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.

Dataset Information

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study.

Introduction

Methods

Results

Conclusions

Publications

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study.

Similar Datasets

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