Association of a single nucleotide polymorphism in Tbx4 with developmental dysplasia of the hip: a case-control study

Abstract

Developmental dysplasia of the hip (DDH), formerly known as congenital dislocation of the hip, comprises a spectrum of abnormalities, including abnormal acetabular shape (dysplasia) and malposition of the femoral head during embryonic, fetal and infantile growth periods. Genetic factors play a considerable role in the pathogenesis of DDH. As a key regulator for the hindlimb outgrowth and identification, Tbx4 may be involved in the aetiology and pathogenesis of DDH. Our objective is to evaluate whether the Tbx4 (rs3744438 and rs3744448) single nucleotide polymorphisms (SNPs) are associated with DDH in Chinese. The Tbx4 SNPs were genotyped in 505 children with DDH and 551 control subjects and their association was evaluated statistically. Rs3744438 was not associated with DDH. Rs3744448 was significantly associated with DDH in the dominant genetic model of males (P=0.039; odds ratio (OR)=0.56; 95% confidence interval (CI)=0.32-0.97) and allele G was significantly lower in patients than controls compared with allele C(P=0.02; OR=0.59; 95% CI=0.37-0.92). After adjusted for gender, we discovered a significant association with hip dislocation in the dominant genetic model when stratified by severity (P=0.03; OR=0.73; 95% CI=0.55-0.97), but not with subluxation and instability. Tbx4 tends to play an important role in the aetiology of DDH.