Transmission disequilibrium between congenital dislocation of the hip and homeobox-containing genes*

Hongwei MA; Yao LU; Jun JIANG; Yueping WANG; Qiwei LI; Yang WANG; Shijun JI

ABSTRACT

BACKGROUND:

Research shows that genetic factors are an important component of the congenital dislocation of the hip(CDH) . However, no susceptibility genes have been identified by now. The homebox-containing (HOX) genes that regulate the embryogenesis and vertebrate limb development may play a role in the pathogenesis of CDH.

OBJECTIVE:

To investigate whether a correlation exists between CDH and the Hox genes.

DESIGN:

Controlled study associated with family.

SETTING:

Department of aevelopmental pediatrics, genetic laboratory, department of pediatric orthopaedics in an affiliated hospital of a university.

PARTICIPANTS:

All the 101 CDH patients and their parents (altogether 303 members) were the in-patients from the Department of Pediatric Orthopaedics of the Second Clinical College of China Medical University; from December 1999 to January 2001. All the patients presented typical clinical manifestations and were diagnosed by X rays and operations for confirmation.

METHODS:

Four microsatellite markers D7S1808, D17S1820, D12S1686 and Hox4EP were selected in the chromosome regions of7p14 - 15, 17q21, 12q13and 2q31 where Hox A, Hox B, Hox C and Hox D genes which regulate the embryonic limb development reside respectively. Genotypes of 303 members in 101CDH families were analyzed by the techniques of polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test(TDT) was performed to analyze the data of genotypes.MAIN OUTCOME

MEASURES:

The genotypes of four microsatellite markers D7S1808, D17S1820, D12S1686 and Hox4EP in every CDH family including one child and parents; transmission disequilibrium test between transmission alleles and non-transmission alleles.

RESULTS:

Transmission disequilibrium was found between CDH and allele 7 of D7S1808(X2 = 6. 045, P = 0. 014) among a total of 10 alleles detected, between CDH and allele 4 of D17S1820(X2 =6. 025, P =0. 014) among a total of 12 alleles detected, between CDH and allele 4 of Hox4Ep (X2 = 6. 461, P =0.011) among a total of 16 alleles detected. But no transmission disequilibrium was found between CDH and D12S1686(X2 = 6. 171,P =0. 965) with 16 alleles detected.

CONCLUSION:

CDH may be related to Hox A, Hox B, Hox D genes, and Hox A, Hox B, Hox D genes may be susceptibility genes in CDH.