Ke Su1, Shuxia Chen1, Jianhong Ye1, Lele Kuang1, Ting Zhang2, Hongyan Wang1,3,4, Xueyan Yang5. 1. The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200438, China. 2. Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China. 3. Institute of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China. 4. Key Laboratory of Reproduction Regulation of NPFPC, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200032, China. 5. The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200438, China. Xueyanyang@fudan.edu.cn.
Abstract
PURPOSE: Transcription factor AP-2 alpha (TFAP2A) is an important transcriptional factor involved in various aspects of embryo development including neural tube closure. Tfap2a deficiency led to the failure of cranial neural-tube closure in mice and other model organisms. However, it remains largely unknown about the relationship between TFAP2A variants and human cranial neural tube defects (NTDs). The aim of this study was to find the association between TFAP2A intronic SNP rs3439413 and NTDs and to explore its function. METHODS: We found an indel polymorphism rs3439413 in TFAP2A intron-5 from our previous target sequencing project. In this study, we validate its association with human NTDs in Shanxi group containing 266 NTD cases and 295 matched controls. Then, we investigated its function on transcriptional activity by dual-luciferase assays and EMSA. RESULTS: The minor allele of rs34396413 significantly increased the risk of NTD in a Han Chinese population of Shanxi Province (P = 0.0082, OR = 1.45, 95%CI = 1.10-1.90), especially the risk of encephalocele for female (P = 0.0064, OR = 2.46, 95%CI = 1.22-4.94). Functional analysis revealed the minor allele of rs34396413 decreases transcriptional activity and attenuates transcription factor binding affinity. CONCLUSION: We have demonstrated that the minor allele of rs34396413 was a risk factor of NTD in the Shanxi group, providing new insight into the study of NTD etiology.
PURPOSE: Transcription factor AP-2 alpha (TFAP2A) is an important transcriptional factor involved in various aspects of embryo development including neural tube closure. Tfap2a deficiency led to the failure of cranial neural-tube closure in mice and other model organisms. However, it remains largely unknown about the relationship between TFAP2A variants and humancranial neural tube defects (NTDs). The aim of this study was to find the association between TFAP2A intronic SNP rs3439413 and NTDs and to explore its function. METHODS: We found an indel polymorphism rs3439413 in TFAP2A intron-5 from our previous target sequencing project. In this study, we validate its association with human NTDs in Shanxi group containing 266 NTD cases and 295 matched controls. Then, we investigated its function on transcriptional activity by dual-luciferase assays and EMSA. RESULTS: The minor allele of rs34396413 significantly increased the risk of NTD in a Han Chinese population of Shanxi Province (P = 0.0082, OR = 1.45, 95%CI = 1.10-1.90), especially the risk of encephalocele for female (P = 0.0064, OR = 2.46, 95%CI = 1.22-4.94). Functional analysis revealed the minor allele of rs34396413 decreases transcriptional activity and attenuates transcription factor binding affinity. CONCLUSION: We have demonstrated that the minor allele of rs34396413 was a risk factor of NTD in the Shanxi group, providing new insight into the study of NTD etiology.
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