Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint osteoarthritis in female Han Chinese

Abstract

Temporomandibular joint osteoarthritis (TMJOA) is a complex disease and has a strong genetic component in its pathogenesis. Experimental evidence suggests the involvement of biological pathway in the disease. This case-control study was designed to investigate whether five common single nucleotide polymorphisms (SNPs) in GDF5, SMAD3, RUNX2, TGFβ1 and CHST11, respectively, are associated with TMJOA in female Han Chinese patients. A total of 240 participants were evaluated comprising 114 female patients diagnosed with TMJOA based on Research Diagnostic Criteria for Temporomandibular Disorders and 126 healthy female controls. The SNPs of the five genes in the genomic DNA were examined by sequencing, and their allelic, genotypic and carriage rate frequency distributions, as well as the triple combination of the risk genotypes, were analysed using the logistic regression model. The SNP in GDF5 or SMAD3 showed significant association with TMJOA, a relatively weak association was observed in RUNX2. In the triple combinational analysis, the risk of TMJOA grew 5·09 times in the patients with five or six risk alleles (P < 0·01). This is the first study to evaluate the association of GDF5, SMAD3, RUNX2, TGFβ1 and CHST11 with TMJOA in female Han Chinese. Our study suggests that the SNPs of genes related to TGFβ family might contribute to the risk of TMJOA.

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].…”

Association between SMAD3 gene rs12901499 polymorphism and knee osteoarthritis in a Chinese population

“…van de Laar et al revealed that mutations in SMAD3 could contribute to increased aortic expression of several key members in the TGF‐β pathway including SMAD3, which showed significant correlation with early‐onset OA. Recently, 5 studies (2 Caucasian studies and 3 Asian studies) explored the association between SMAD3 rs12901499 polymorphism and risk of OA, but with conflicting results . Some studies have shown that SMAD3 rs12901499 polymorphism was associated with OA risk .…”