A functional indel polymorphism rs34396413 in TFAP2A intron-5 significantly increases female encephalocele risk in Han Chinese population
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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.
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.
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.
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.
KeywordsNeural tube defects TFAP2A Intronic variant rs34396413 Enhancer
We sincerely thank all the patients and control individuals for their participation in this study.
This work is supported by grants from the National Key Basic Research Program of China (2016YFC1000502 to X. Yang and H. Wang), the National Natural Science Foundation of China (81472050 to X. Yang and 81430005, 31521003, 81741048 to H. Wang), and Open project of National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices (2016KF04 to X Yang).
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
All procedures performed in studies involving human participants were approved by the Ethics Committee of the School of Life Sciences, Fudan University.
Research involving human participants and animals
This article did not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in this study.
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