DNA methyltransferase 3A promoter polymorphism is associated with the risk of human spontaneous abortion after assisted reproduction techniques and natural conception
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The aim of this study was to explore the association of the DNA-methyltransferase (DNMT)-3A and DNMT3B promoter polymorphisms with the risk of human spontaneous abortion after assisted reproduction techniques (ARTs) and natural conception.
We collected tissues from women who underwent abortion procedures: (a) chorionic villus samples (CVS) and muscle samples (MS) from spontaneous abortions conceived by ART and natural cycle (study group), n = 152; and (b) CVS and MS from normal early pregnancy and second trimester (control group), n = 155. The single-nucleotide polymorphism (SNP) −448A > G in the DNMT3A promoter region and −149C/T polymorphism of DNMT3B were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing.
The allele frequency of −448A among pregnancy loss group and control group was 34.2 % vs. 16.5 %, respectively. Compared with GG carriers, the DNMT3A −448AA homozygotes had an about 16-fold increased risk of spontaneous abortion [odds ratio (OR) = 16.130, 95 % confidence interval (CI), 3.665–70.984], and AG heterozygotes had an OR of 2.027 (95 % CI, 1.247–3.293). However, the distribution of −448A > G in individuals derived from ART pregnancies was not statistically significantly compared with those derived from spontaneous pregnancies (P = 0.661). For DNMT3B, we observed genotype frequencies of 100 % (TT) in the study group and the control group.
The DNMT3A −448A > G polymorphism may be a novel functional SNP and contribute to its genetic susceptibility to spontaneous abortion in Chinese women, and ART may not affect the distribution of −448A > G in pregnancy loss and normal pregnancy. The observed TT genotype of DMNT3B suggests that this is the predominant genotype of this population. The findings provide new insights into the etiology of human spontaneous abortion.
KeywordsDNA methylation Spontaneous abortion DNA-methyltransferase Single-nucleotide polymorphisms Assisted reproductive technology
The authors gratefully acknowledge the technical support and valuable suggestions of all members from the Research Center of Clinical Medicine of Nanfang Hospital, and the help of the staff from the Department of Gynecology and Obstetrics in Nanfang Hospital in sample collection.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.
This study was funded by the National Natural Science Foundation of China (no. 81170574 and no. 31371517) and High-level Project Matching Foundation of Nanfang Hospital, Southern Medical University (G201206).
Conflict of Interest
The authors declare that they have no competing interests.
- 3.Adalsteinsson BT, Ferguson-Smith AC. Epigenetic control of the genome-lessons from genomic imprinting. Genes (Basel). 2014;5(3):635–55.Google Scholar
- 36.Camprubi C, Iglesias-Platas I, Martin-Trujillo A, Salvador-Alarcon C, Rodriguez MA, Barredo DR, et al. Stability of genomic imprinting and gestational-age dynamic methylation in complicated pregnancies conceived following assisted reproductive technologies. Biol Reprod. 2013;89(3):50.CrossRefPubMedGoogle Scholar
- 42.Wang C, Jia Z, Cao D, You L, Jin M, Wu X, et al. Polymorphism of DNA methyltransferase 3b and association with development and prognosis in gastric cancer. PLoS One. 2015;10(8), e134059.Google Scholar