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

<b><i>Background:</i></b> 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 <i>ZBED5/GALNT18</i> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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, <i>p</i> = 0.0327; and GG/AG vs. AA: adjusted OR = 1.38, 95% CI = 1.02-1.87, <i>p</i> = 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, <i>p</i> = 0.0133), while AA in nonrelapsed groups (OR = 0.70, 95% CI = 0.53-0.92, <i>p</i> = 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, <i>p</i> = 0.8906). <b><i>Conclusions:</i></b> 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.