Association between GDF5+104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
Authors: Jiang, Dong; Hao, Zengtao; Fan, Dongsheng; Guo, Wen; Xu, Pengcheng; Yin, Chao; Wen, Shuzheng; Wang, Jihong
Abstract
Background: Osteoarthritis (OA) is a degenerative joint disease with a complex genetic background. Variants in growth differentiation factor 5 (GDF5) have been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The present study aimed to assess the association between the GDF5 + 104T/C polymorphism and the susceptibility of the knee to OA through a meta-analysis of available case-control studies. Methods: The PubMed and Science Direct citation databases were used to search electronic literature in order to identify studies published between January 2007 and July 2016 that evaluated the association between the GDF5 + 104T/C polymorphism and the susceptibility of the knee to OA. Different genetic models were used to assess the pooled and stratified data. Results: A positive association was found in all pooled studies (OR = 0.808, 95 % CI = 0.754-0.866, P < 0.001). Regarding genotypes, significant associations were found using a dominant model (OR = 0.777, 95 % CI = 0.708-0.852, p < 0.001), a recessive model (OR = 0.723, 95% CI = 0.623-0.839, p < 0.001), and an additive model (CC vs TT OR = 0.648, 95 % CI = 0.552-0.760, p < 0.001; CC vs CT OR = 0.801, 95 % CI = 0.685-0.936, p = 0.005). Meta-analysis data were stratified by ethnicity, and the GDF5 C allele was found to be positively associated with OA of the knee in both Caucasians and Asians, as were the GDF5 TC and CC genotypes. In addition, using an additive model, the CC genotype was found to be significantly associated with OA of the knee in both Caucasians and Asians when comparing CC vs TT genotypes, but not in Caucasians when comparing TT vs CT genotypes. Conclusions: Meta-analysis results indicated that the GDF5 + 104T/C polymorphism is a protective factor for OA among Caucasian and Asian populations.
Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology-a genetic association study
RHEUMATOLOGY
Authors: Posthumus, Michael; Collins, Malcolm; Cook, Jill; Handley, Christopher J.; Ribbans, William J.; Smith, Roger K. W.; Schwellnus, Martin P.; Raleigh, Stuart M.
Abstract
Methods. One hundred and seventy-one subjects (58 AUS and 112 SA) with Achilles tendon pathology (ATP group) and 235 (142 AUS and 96 SA) asymptomatic control (CON group) subjects were genotyped for the selected SNPs using custom-designed Taqman assays. A chi(2)-analysis or Fisher's exact test was used to analyse any differences in the genotype and allele frequencies. Significance was accepted when P < 0.05. Results. There were no significant TGFB1 rs1800469 genotype (P = 0.491) or allele (P = 0.400) frequency differences between the ATP and CON groups. The TT genotype of the GDF5 rs143383 variant was significantly over-represented in the ATP group of the AUS cohort [P = 0.011; odds ratio (OR) = 2.24; 95% CI 1.21, 4.16], and when the AUS and SA cohorts were combined (P = 0.004; OR = 1.82; 95% CI 1.23, 2.74). Conclusions. In conclusion, this study suggests that individuals with a TT genotype of the functional GDF5 rs143383 variant have twice the risk of developing ATP. This finding highlights a role of GDF-5 in the pathogenesis of Achilles tendon pathology.