Association of Polymorphism in Locus of rs274503 (ZBED5/GALNT18) with the Risk of Idiopathic Clubfoot in Chinese Children: An 11-Center Case-Control Study.

Abstract

Background: Idiopathic clubfoot (IC) can be corrected initially using the Ponseti method, but still there is a high recurrence rate. The etiology of IC may include many undetermined genetic and environmental factors. Single nucleotide polymorphism of rs274503 in ZBED5/GALNT18 has been found to be associated with IC in Caucasian children. Therefore, we decided to investigate the association between this polymorphism and the risk of IC in the Chinese population. Methods: We conducted an 11-center case-control study of 516 patients with IC and 661 IC-free children. The rs274503 (A>G) polymorphism was genotyped using TaqMan. Odds ratios (ORs) and adjusted ORs, as well as 95% confidence intervals (CIs) and adjusted 95% CIs, were calculated to explore the association between rs274503 polymorphism and IC risk. Results: G of rs274503 was found to be associated with increased IC risk (AG vs. AA: adjusted OR = 1.40, 95% CI = 1.03-1.92, p = 0.0327; and GG/AG vs. AA: adjusted OR = 1.38, 95% CI = 1.02-1.87, p = 0.0357) after adjusting for age and sex. Furthermore, the risk effect of rs274503 GG/AG with IC was observed in patients with bilateral feet (adjusted OR = 1.68, 95% CI = 1.12-2.54, p = 0.0133), while AA in nonrelapsed groups (OR = 0.70, 95% CI = 0.53-0.92, p = 0.0095) in the stratified analysis. However, the association was not significant in the recessive model of G (GG vs. AA/AG: adjusted OR = 1.06, 95% CI = 0.44-2.58, p = 0.8906). Conclusions: The rs274503 polymorphism is associated with the risk of clubfoot occurrence. G of rs274503 appeared to be a risk factor of IC as it may increase the bilateral case rate. However, further studies are required to confirm these findings.