A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population

Abstract

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.

Occupational and genetic risk factors for osteoarthritis: A review

“…A meta-analysis of data from Europe and Asia (more than 11 000 individuals) confirmed the association between rs143383 SNP and knee OA [100]. In recent studies, the TT genotype of the rs143383 SNP was found to be associated with an increased risk of knee OA in a Thai population [101] and the T allele of the same SNP was associated with a 17% increased risk of knee OA in Caucasians [102]. …”

A Single Nucleotide Polymorphism in the GDF5 Gene (rs143383) may contribute to the Increased Risk of Osteoarthritis and Lumbar Disc Degeneration: an Updated Meta-Analysis

“…Moreover, OA cases were defined with different criteria in different studies, which might be one of sources of observed heterogeneity. Some studies defined their patients using the K/L classification and/or ACR criteria [29][30][31][32][33][34][35]37,[39][40][41][42][43], while other studies defined their patients using the TKR [28,36,38]. This discrepancy on those key characteristics of the participants，such as age and BMI, might also lead to the heterogeneity [34].…”

“…The remaining studies (n=38) were reviewed and additional 22 studies were excluded for not being case-control or cohort studies (n=6), not relevant to the GDF5 gene (n=3), not related to OA or LDD (n=7), or unavailable genotyping data (n=6). In the final analysis, there were 15 articles that were combined to perform an association analysis of rs143383 with OA and/ or LDD [28][29][30][31][32][33][35][36][37][38][39][40][41][42][43].The characteristics of these included articles were presented in Table 1. All the studies conformed to HWE in the control group.…”

“…OA and/or LDD [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Most studies reported a positive association between rs143383 polymorphism and the risk of OA and LDD [28,29,[31][32][33][34][35][36][37][38][40][41][42][43], while few studies generated negative results [30,39].…”

“…Most studies reported a positive association between rs143383 polymorphism and the risk of OA and LDD [28,29,[31][32][33][34][35][36][37][38][40][41][42][43], while few studies generated negative results [30,39]. Two previous meta-analyses have reported that the rs143383 polymorphism was important in the progression of knee OA [44,45].…”