Association of GDF-5 rs143383 polymorphism with radiographic defined knee osteoarthritis: A systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Aghili K
PROVIDER: S-EPMC6128174 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
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Association of GDF-5 rs143383 polymorphism with radiographic defined knee osteoarthritis: A systematic review and meta-analysis.
Aghili Kazem K Sobhan Mohammad Reza MR Mehdinezhad-Yazdi Masoud M Jafari Mohammadali M Miresmaeili Seyed Mohsen SM Rastegar Shohreh S Mazaheri Mahta M Neamatzadeh Hossein H
Journal of orthopaedics 20180824 4
<h4>Objective</h4>To assess the association of GDF-5 rs143383 polymorphism with radiographic defined knee osteoarthritis (OA), a systematic review and meta-analysis was conducted.<h4>Methods</h4>A total of 17 relevant case-control studies with 7424 cases and 11,310 controls was collected from several electronic databases up to June 2018.<h4>Results</h4>The pooled results showed that GDF-5 rs143383 polymorphism was significantly associated with radiographic defined knee OA in overall and stratifi ...[more]
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Project description:BackgroundPrevious studies investigating the association between GDF5 rs143383 polymorphism and knee osteoarthritis (OA) have suggested stronger associations in Asians than Caucasians, but limitations on the amount of available data have meant that a definitive assessment has not been possible. Given the availability of more recent data, the aim of this meta-analysis was to determine the overall association between GDF5 rs143383 polymorphism and knee OA and whether the association varies by ethnicity.MethodsSearches of Medline, Embase, and ISI Web of Science were conducted up to July 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association between the GDF5 polymorphism and knee OA risk.ResultsA total of 20 studies with 23,995 individuals were included. There were weak but significant associations present between the GDF5 polymorphism and knee OA at the allele level (C vs. T: OR =0.85, 95% CI = 0.80-0.90) and genotype level (CC vs. TT: OR = 0.73; CT vs. TT: OR = 0.84; CC/CT vs. TT: OR = 0.81; CC vs.Ct/ttOR = 0.81) in the overall population. In the subgroup analysis by ethnicity, we observed a strong significant association (OR = 0.60 to 0.80, all P <0.05) in Asian population and weaker associations (OR =0.78 to 0.87, all P <0.05) in Caucasian population; however marked heterogeneity was detected in all models except for CC vs. TT (I2 = 12.9%) and CC vs. CT + TT (I2 = 0.0%) in Asians.ConclusionsThese results strongly suggest that the C allele and CC genotype of the GDF5 gene are protective for knee OA susceptibility across different populations.
| S-EPMC4265459 | biostudies-literature
Project description:BackgroundOsteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis.ObjectivesWe examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility.MethodsAll relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI).ResultsThe meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population.ConclusionWe found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.
| S-EPMC10563324 | biostudies-literature
Project description:Objective:To evaluate the association of ESR1 rs2234693 and rs9340799 polymorphisms with radiographic defined knee osteoarthritis (OA), a case-control and meta-analysis was performed. Methods:A total of 25 case-control studies with 7,144 cases and 8,468 controls with were included. Results:There was a significant association between rs2234693 polymorphism and radiographic knee OA under heterozygote model (CT vs. TT: OR?=?1.164, 95% CI 1.053-1.286, p?=?0.003). However, there was no association between rs9340799 and radiographic knee OA. In subgroup analysis by ethnicity, risk estimates were not augmented. Conclusions:Our results showed that the ESR1 rs2234693 polymorphism might be associated with radiographic defined knee OA, but not rs9340799.
| S-EPMC6411600 | biostudies-literature
Project description:BackgroundA few months ago, the Bioscience Reports journal showed that growth differentiation factor 5 (GDF5) rs143383 genetic polymorphism increases the susceptibility of knee osteoarthritis (KOA), but previous studies' results have debates about available data. Considering the availability of more recent data, we focus on clarifying the relationship of KOA and GDF5 rs143383 genetic polymorphism by a meta-analysis of case-control trial data.MethodsThe eligible studies from the time of database established to Oct. 2019 were collected from PubMed, Springer, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang library. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate the association between these polymorphisms and KOA risk. The meta-analysis was completed by STATA 18.0 software.ResultsA total of 196 studies were collected, 16 of them included in final meta-analysis (7997 cases and 12,684 controls). There was significant association between GDF5 rs143383 polymorphism and KOA in all genetic models (for Allele model (C versus T): OR = 0.84 (95% CI = 0.76-0.91); dominate model (CC+CT versus TT): OR = 0.80 (95% CI = 0.72-0.90); recessive model (CC versus CT+TT): OR = 0.79 (95% CI = 0.68-0.92); heterozygote model (CT versus CC+TT): OR = 0.89 (95% CI = 0.80-0.97); homozygous model (CC versus TT): OR = 0.71 (95% CI = 0.60-0.85)). In the subgroup analysis, we obtained the results that there is no significance among Asians.ConclusionGDF5 rs143383 genetic polymorphism increases the risk of KOA among Caucasians; CC genotype and C allele are protective factors for the susceptibility of KOA among Caucasians.
| S-EPMC7488690 | biostudies-literature
Project description:ObjectiveOsteoarthritis (OA) is a multi-factorial disease and genetic factor is one of the important etiologic risk factors. Various genetic polymorphisms have been elucidated that they might be associated with OA. Recently, several studies have shown an association between Growth Differentiation Factor 5(GDF5) polymorphism and knee OA. However, the role of genetic predisposing factor in each ethnic group cannot be replicated to all, with conflicting data in the literatures. Therefore, the aim of this study was to investigate the association between GDF5 polymorphism and knee OA in Thai population.Materials and methodsOne hundred and ninety three patients aged 54-88 years who attended Ramathibodi Hospital were enrolled. Ninety cases with knee OA according to American College of Rheumatology criteria and one hundred and three cases in control group gave informed consent. Blood sample (5 ml) were collected for identification of GDF5 (rs143383) single nucleotide polymorphism by PCR/RFLP according to a standard protocol. This study protocol was approved by the Ethics Committee on human experimentation of Ramathibodi Hospital Faculty of Medicine, Mahidol University. Odds ratios (OR) and 95% confidence intervals were calculated for the risk of knee OA by genotype (TT, TC and CC) and allele (T/C) analyses.ResultsThe baseline characteristics between two groups including job, smoking and activity were not different, except age and BMI. The entire cases and controls were in Hardy-Weinberg equilibrium (p > 0.05). The OA knee group (n = 90) had genotypic figure which has shown by TT 42.2% (n = 38), TC 45.6% (n = 41) and CC 12% (n = 11), whereas the control group (n = 103) revealed TT 32% (n = 33), TC 45.6% (n = 47), and CC 22.3% (n = 23), respectively. Genotypic TT increased risk of knee OA as compared to CC [OR = 2.41 (P = 0.04, 95%CI = 1.02-5.67)]. In the allele analysis, the T allele was found to be significantly associated with knee OA [OR = 1.53 (P = 0.043, 95%CI = 1.01-2.30)].ConclusionThese data suggested that GDF5 polymorphism has an association with knee OA in Thai ethnic. This finding also supports the hypothesis that OA has an important genetic component in its etiology, and GDF5 protein might play important role in the pathophysiology of the disease.
| S-EPMC3189142 | biostudies-literature
Project description:Background and objective Osteoarthritis (OA) is influenced by genetics and environmental factors, including vitamin D deficiency. This study aimed to investigate the association between vitamin D levels, growth/differentiation factor 5 (GDF-5) gene polymorphism, and serum GDF-5 in obese females with knee OA (KOA) in Saudi Arabia. Methodology The study enrolled 60 female patients with OA and 60 healthy females as controls. Blood samples were collected to evaluate the GDF-5 T>C (rs143383) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study also measured serum levels of vitamin D, GDF-5, calcium, uric acid, lipid profiles, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and assessed the participants' BMI. Results The study demonstrated that KOA patients had reduced vitamin D levels in their bodies, along with GDF-5 and calcium. However, they had increased levels of uric acid, lipid profile, CRP, and ESR. Strong correlations were observed between vitamin D levels, lipid profile, CRP, ESR, BMI, GDF-5 gene polymorphisms, and GDF-5 protein. Genotype analysis showed KOA patients had TT (30%), TC (50%), and CC (20%) genotypes, while the control group showed TT (22%), TC (35%), and CC (43%) genotypes. Allele analysis revealed a noteworthy association between the T allele and KOA; the C allele was more common in the control group. Conclusions The study findings provide valuable insights into the association of vitamin D levels with GDF-5 T>C (rs143383) polymorphism, GDF-5 protein, and inflammatory markers in obese Saudi females with KOA. These findings suggest potential associations between these biomarkers and the pathogenesis or progression of KOA.
| S-EPMC10698833 | biostudies-literature
Project description:ObjectiveTo examine the cross-sectional associations between dietary magnesium (Mg) intake and radiographic knee osteoarthritis (OA), joint space narrowing (JSN), and osteophytes (OST) respectively.MethodsA total of 1626 subjects were included in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade 2 in at least one leg. JSN and OST were assessed individually according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the various associations after adjusting for potentially confounding factors.ResultsThe relative odds of radiographic knee OA were decreased by 0.53 times in the third quintile of Mg intake [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.28-1.01], 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.17-0.94) and 0.34 times in the fifth quintile (OR 0.34, 95% CI 0.11-1.00) compared with those in the lowest quintile, while P for trend was 0.111. The relative odds of JSN were decreased by 0.49 times in the third quintile of Mg intake (OR 0.49, 95% CI 0.28-0.88) and 0.37 times in the fifth quintile (OR 0.37, 95% CI 0.14-0.98) compared with those in the lowest quintile, while P for trend was 0.088. There was no significant relationship between dietary Mg intake and the presence of OST.ConclusionsThe findings of this cross-sectional study indicate that Mg intake is inversely associated with radiographic knee OA and JSN. It supports potential role of Mg in the prevention of knee OA.Level of evidenceLevelIII, cross-sectional study.
| S-EPMC4444049 | biostudies-literature
Project description:OBJECTIVE:Studies have assessed the association between aspartic acid (D)-repeat polymorphism in the gene encoding Asporin (ASPN) and knee osteoarthritis (KOA) risk, but the results were inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between ASPN gene D-repeat polymorphism and KOA risk. METHODS:Eligible studies were identified by searching several electronic databases for relevant reports published before September 2016. The pooled odds ratios (ORs) for the association between ASPN polymorphism and KOA and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed-effect model. RESULTS:A total of eleven case-control studies in ten publications with 4610 KOA cases and 3621 controls were included for the ASPN D-repeat polymorphism. Overall, no significant association was detected for D14 allele carrier (D14 vs. D13: OR = 1.10, 95% CI = 0.90-1.36, p = 0.32). Meta-analysis of D14 vs. other alleles and D13 vs. other alleles showed the same pattern of KOA association as the D14 vs. D13 (OR = 1.30, 95% CI = 1.00-1.70, p = 0.06; OR = 0.93, 95% CI = 0.82-1.06, p = 0.33, respectively). Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of KOA was found in the European and Asians populations (OR = 1.05, 95% CI = 0.91-1.21, p = 0.49; OR = 0.98, 95% CI = 0.78-1.23, p = 0.88, respectively). CONCLUSIONS:The present meta-analysis suggests that the ASPN D-repeat polymorphism is not associated with an increased KOA risk. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings. LEVEL OF EVIDENCE:Level III diagnostic study.
| S-EPMC6197333 | biostudies-other
Project description:Background and purpose - Knee extensor (KE) muscle weakness is a modifiable feature commonly observed in individuals with knee osteoarthritis (KOA) and constitutes a potential target for patient-specific interventions. Therefore, in this study, we explored whether KE weakness is associated with radiographic (medial and/or lateral) KOA progression and how this relationship differs depending on frontal plane knee alignment and sex. Patients and methods - We studied 3,075 knees (1,961 participants, 58% female) from the Osteoarthritis Initiative with radiographic Kellgren-Lawrence grade 1-3. Peak KE torque (Nm/kg) was assessed at baseline, and progression defined as fixed-location joint space width loss (? 0.7mm) in medial and lateral tibiofemoral compartments from baseline to 4-year follow-up. Knee-based generalized estimating equations, stratified by alignment (malaligned vs. neutral), estimated the relative risk (RR) of progression for those in the lowest (and middle) vs. highest KE torque group (split by tertiles). Secondary analyses explored whether this relationship was compartmental- or sex-specific. Results - Being in the lowest (or middle) compared with the highest torque group increased the risk of progression in neutrally aligned knees (relative risk [RR] 1.2 [95% CI 1.0-1.4]; and 1.2 [CI 1.0-1.4], respectively), but not after adjusting for age, sex, BMI, pain, and radiographic severity. In secondary analyses, women with neutral alignment in the lowest compared with the highest torque group had significantly increased risk of lateral compartment progression independent of age, BMI, disease severity, and pain (RR 1.3 [CI 1.0-1.8]). No association was observed between KE torque and KOA progression in men, irrespective of alignment. Interpretation - These results identify a potentially important clinical phenotype: KE weakness may be a more important risk factor for radiographic KOA progression in women without knee malalignment.
| S-EPMC6066769 | biostudies-literature
Project description:ObjectiveA major barrier to genetic studies of osteoarthritis (OA) is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from 4 well-characterized North American cohorts, and we performed replication analysis of previously reported OA loci.MethodsWe performed meta-analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definite osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead meta-analysis variants (P ≤ 1 × 10-4 ) from stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis.ResultsLead variants from stage 1, representing 49 unique loci, were analyzed in stage 2; none met genome-wide significance in the combined analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3) with nominal significance (P < 0.05), which was also our top finding in the combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.79-0.91], P = 3.02 × 10-6 ). We observed nominally significant associations (P < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI 1.04-1.21], P = 2.13 × 10-3 ), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 × 10-3 ).ConclusionThese findings provide suggestive evidence of a novel knee OA locus and confirm previously reported associations in GDF5, CHST11, and FTO.
| S-EPMC5274579 | biostudies-literature