Evaluation of regulatory genetic variants in POU5F1 and risk of congenital heart disease in Han Chinese.
OCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%-5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10(-6)]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yuan
Y
Lin
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Chenyue
C
Ding
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Kai
K
Zhang
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Bixian
B
Ni
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Min
M
Da
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Liang
L
Hu
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Yuanli
Y
Hu
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Jing
J
Xu
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Xiaowei
X
Wang
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yijiang
Y
Chen
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Xuming
X
Mo
Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yugui
Y
Cui
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongbing
H
Shen
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
Jiahao
J
Sha
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Jiayin
J
Liu
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Zhibin
Z
Hu
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006330:Heart Defects, Congenital / Q000209:etiology*; D006801:Humans; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human