The Genetic Study Of Developmental Dysplasia Of The Hip

Objective: The aim of this study is to investigate the potential candidate genes of DDH, we have selected several SNPs from three groups of different genes, including5’end of HOXD gene cluster, DLX3, 4, 5 and hip geometry related genes, respectively.Time-of-flight Mass Spectrometry(MALDI-TOF MS) was used to perform genotyping analysis. Compared with healthy controls and the public database, we would like to discuss the association between these SNPs and the development of DDH. We hope our study can help shed light on the complex genetic etiology of DDH and provide more theoretical evidences for early diagnosis and prevention of DDH.Methods: 1. For this study, combining the mechanism of limb development and the main pathological changes of DDH, we speculated that the 5’end of HOXD gene cluster may be candidate genes for DDH. Nine SNPs were picked in 4 candidate genes, including HOXD9, HOXD10, HOXD11 and HOXD12. The study population contains a total of 210 cases with DDH and 174 healthy controls. MALDI-TOF MS was used to perform genotyping analysis. 2. For this study, combining the susceptibility loci for DDH which have been detected by linkage analysis, biological function of known genes in these areas and the main pathological changes of DDH,we speculated that DLX 3, DLX4 and DLX5 may be candidate genes for DDH. Eight SNPs were picked from these three genes. The study population contains a total of192 cases with DDH and 188 healthy controls. MALDI-TOF MS was used to perform genotyping analysis. 3. This Study based on the past research in the field of bone and the hip geometry related genome-wide association analysis(GWAS), we speculated that genes which were associated with bone geometry may be candidate genes for DDH. Nine SNPs were picked in 5 candidate genes, including VAMP1, ZNF366,PHACTR1, RTP3 and PLCL1. The study population contains a total of 192 cases with DDH and 188 healthy controls. MALDI-TOF MS was used to perform genotyping analysis.Results: 1. Among the 9 SNPs of 5’end of HOXD gene cluster, we found five were closely related to the development of DDH. They were rs711819 in HOXD9 gene,rs7601234 in HOXD10 gene, rs6745764 and rs711815 in HOXD11 gene, and rs35817516 in HOXD12 gene. The other 4 SNPs were not associated with DDH, they were rs711822 in HOXD9 gene, rs78466921 and rs4972803 in HOXD10 gene, and rs711812 in HOXD12 gene. 2. Among the 8 SNPs, we found five were closely related to the development of DDH. They were rs2278163, rs12452477 and rs2303466 in DLX3 gene, rs1058564 and rs3760415 in DLX4 gene. The other three SNPs were not associated with DDH, they were rs12077335, rs9769385 and rs35273378 in DLX5 gene. 3. Among the 9 SNPs, we found four were closely related to the development of DDH. They were rs10492096 in VAMP1 gene, rs10515148 in ZNF366 gene,rs4715166 in PHACTR1 gene and rs3771362 in PLCL1 gene.The other five SNPs were not associated with DDH, they were rs10514713 and rs7430431 in RTP3 gene,rs4850820, rs4850833 and rs9789480 in PLCL1 gene.Conclusion: 1. For the first time, we found that rs711819 in HOXD9 gene, rs7601234 in HOXD10 gene, rs6745764 and rs711815 in HOXD11 gene, and rs35817516 in HOXD12 gene were closely related to the development of DDH. This research is the first to show that 5’end of HOXD gene cluster were associated with DDH. 2. For the first time, we found that rs2278163, rs12452477 and rs2303466 in DLX3 gene,rs1058564 and rs3760415 in DLX4 gene were closely related to DDH. This research is the first to show that DLX3 and DLX4 were associated with DDH. 3. For the first time, we found that rs10492096 in VAMP1 gene, rs10515148 in ZNF366 gene,rs4715166 in PHACTR1 gene and rs3771362 in PLCL1 gene were closely related to DDH. This research is the first to show that hip geometry related genes were associated with DDH.