Dataset Information

Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects.

ABSTRACT: BACKGROUND: Previous 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. METHODS: Searches 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. RESULTS: A 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/TT: OR =?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. CONCLUSIONS: These results strongly suggest that the C allele and CC genotype of the GDF5 gene are protective for knee OA susceptibility across different populations.

SUBMITTER: Pan F

PROVIDER: S-EPMC4265459 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects.

Pan Feng F Tian Jing J Winzenberg Tania T Ding Changhai C Jones Graeme G

BMC musculoskeletal disorders 20141202

<h4>Background</h4>Previous 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 varie ...[more]

PMID: 25467786

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Project description:The association between growth differentiation factor 5 (GDF5), single nucleotide polymorphism (SNP) rs143383 and lumbar disc degeneration (LDD) was investigated. A total of 210 patients with LDD (observation group) and 320 patients without lumbar diseases (control group) diagnosed in Shanghai General Hospital of Nanjing Medical University from August 2013 to March 2017 were randomly selected. Then, deoxyribonucleic acid (DNA) was extracted from the blood of each patient, and Taq-man fluorescent quantitative polymerase chain reaction (qPCR) technique was used to detect rs143383 in GFD5 gene. The frequency of different genotypes in observation group and control group was counted, and the associations between different SNP genotypes and the incidence of LDD were analyzed. Good genotyping results were found in both LDD patient group and control group. There were no significant differences in distribution frequency of TT and TC genotypes at site rs143383 between LDD patient group and control group (P>0.05), but the distribution frequency of CC genotype at site rs143383 in LDD patient group had a statistically significant difference from that in control group (P<0.05). In dominant models, odds ratio (OR) of (TC+CC/TT) was 1.195 (P=0.532). In recessive models, OR of (CC/TT+TC) was 4.333 (P=0.028). In co-dominant models, ORs of (TC/TT) and (CC/TT) were 0.967 and 4.43, respectively (P=0.99). The differences in 3 genotypes showed no statistical significance among different pathological grades (Grade I to V) (χ2=1.034, P=0.998), and there was no statistically significant difference in T and C (χ2=0.012, P=0.999). Pathological grades in dominant models, recessive models and over dominant models were analyzed, and no statistically significant difference was found (P>0.05). In conclusion, CC mutant type at rs143383 in GDF5 gene has a strong association with the incidence of LDD, and a high prevalence risk, but it has no evident correlation with pathological grades.

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.

Project description:OBJECTIVE:GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. METHODS:Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. RESULTS:A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09-1.22]) (P=9.4x10(-7)), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P=0.016]) or absent (for OA of the hand [P=0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P=0.019). CONCLUSION:Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.

Dataset Information

Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects.

Publications

Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects.

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