Interaction between GDF5 gene polymorphisms and environment factors increased the risk of knee osteoarthritis: a case–control study

Abstract

Using a case–control design, we assessed the association between single nucleotide polymorphisms (SNPs) of growth and differentiation factor 5 (GDF5)/rs143383 gene and interaction with environments and knee osteoarthritis (KOA). We recruited 288 KOA patients from the First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was significant difference in genotype distribution between case group and control group (χ2 = 22.661, P=0.000). The minor C allele was significantly higher in the case group than that in the control group (20.5 vs 8.1%, P=0.000, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.29–2.03). Significant differences were also observed in other gene models. For age, all models show significant differences (P<0.05) for those whose age was more than 60 years, and no significant difference was observed for those under 60 years. For non-smoking group, there were significant differences between case group and control group, and for smoker, significance level was found in TT compared with CC and allele gene models. Patients with drinking and Bbody mass index (MI )≥ 24 also showed significant relationship between rs143383 and osteoarthritis (OA) under the following models: TT vs CC (P=0.000, P=0.018), TT/CT vs CC (P=0.043), TT vs CT/CC (P=0.000, P=0.009), and T vs C (P=0.024, P=0.000). Other gene models indicated no significance (P>0.05). Our results revealed a possible genetic association between GDF5 and KOA, and the TT genotype of rs143383 increased the risk of KOA in Chinese Han population. The interaction between GDF5 gene and drinking, smoking, and obesity further increased the risk of KOA.

Association between Growth Differentiation Factor 5 rs143383 Genetic Polymorphism and the Risk of Knee Osteoarthritis among Caucasian But Not Asian: A Meta-analysis

“…On the one hand, previous literatures have said that GDF 5 rs143383 polymorphisms C allele is a protective factor for the susceptibility of knee osteoarthritis among Caucasian populations (OR=0.74, P<0.001) and Asian populations (OR=0.87, P=0.004) [9]. On the other hand, Sujie Zhang et al holds that interaction GDF 5 rs143383 polymorphisms T allele increases the risk of knee osteoarthritis among Asian (OR=1.62, P<0.001) [5]. But now our research shows that GDF 5 rs143383 polymorphisms are only relate to knee osteoarthritis among Caucasian populations by subgroup analysis, not Asian populations.…”

“…Sixteen articles [5,11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28], including separate 20 studies (7997 cases and 12684 controls), finally have collected in the meta-analysis from 196 studies, which process is showed in Fig 1. All studies' details, including first author name; year of publication; ethnicity; country; sex; gender ration; evaluation of quality (NOS); HWE; study design; genotyping method and mean age, put into the Table 1.…”

Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: a meta-analysis

“…Knee osteoarthritis is a multi-factorial disease, and its pathogenesis is currently unclear. Current studies have shown that smoking, diet, exercise, and genes are all associated with osteoarthritis [5]. The diagnosis of knee osteoarthritis is currently mainly diagnosed by imaging.…”

“…Growth differentiation factor 5 (GDF5) rs143383 genetic polymorphisms is the association of the susceptibility of knee osteoarthritis reported in Bioscience Reports [5]. GDF5, also known as cartilage derived morphogenetic protein 1 (CDMP1), is an extracellular signaling molecule that participates in the development maintenance and repair of bone, cartilage, and other tissues of the synovial joint, with penetrant and rare deleterious mutations of the GDF5 gene resulting in dominant skeletal defects [6].…”

“…Although the association of the risk of knee osteoarthritis and GDF5 rs143383 genetic polymorphisms has been described in several meta-analyses [8][9][10][11][12], several recent trials also reported the risk of knee osteoarthritis and GDF5 rs143383 genetic polymorphisms [4][5][6]. On the other hand, prior meta-analyses have some limitations, such as low quality and lacking enough studies.…”