Association between the aspartic acid D-repeat polymorphisms and osteoarthritis susceptibility: An updated systematic review and meta-analyses

OBJECTIVES: Association between the D-repeat of asporin (ASPN) gene and osteoarthritis (OA) was still inconsistent. We performed this meta-analysis to systematically assess the D-repeat polymorphisms in OA susceptibility. METHODS: Relevant studies were enrolled by searching databases. Odd ratios (ORs) with 95% confidence intervals (95% CIs) were used for evaluating the association between ASPN gene and OA. Heterogeneity was calculated using the Q statistic, and three different subgroup analyses were performed on ethnicity, gender, and OA positions respectively. False discovery rate (FDR) was applied to regulate the multiple comparisons. RESULTS: Twelve qualified articles involving 5190 OA patients and 5167 healthy controls were included. With D13 polymorphism, Caucasian male patients have low OA susceptibility (P = .008, P(FDR) = .024, OR [95% CI] = 0.83 [0.73–0.95]). As to D14 polymorphism, all male patients (P = .0004, P(FDR) = .001, OR [95% CI] = 1.38 [1.15–1.64]), Asian male patients (P = .01, P(FDR) = .01, OR [95% CI] = 1.72 [1.11–2.66]), and Caucasian male patients (P = .005, P(FDR) = .001, OR [95% CI] = 1.32 [1.09–1.60]) have high OA susceptibility. In the pooled-population of KOA with D14 polymorphism, overall male patients (P = .03, P(FDR) = .045, OR [95% CI] = 1.35 [1.02–1.78]) and Asian male patients (P = .01, P(FDR) = .03, OR [95% CI] = 1.72 [1.11–2.66]) have high OA risk. With D16 polymorphism, Latin America patients may have high OA risk (P = .04, P(FDR) = .15, OR [95% CI] = 1.43 [1.02–2.01]). CONCLUSION: Our results suggest that D-repeat of ASPN gene is mainly associated with male patients. The D13 polymorphism plays a protective role for OA in Caucasians male individuals while D14 plays a risk factor for KOA in male patients.