DNA methyltransferase 3A promoter polymorphism is associated with the risk of human spontaneous abortion after assisted reproduction techniques and natural conception.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Yudong
Y
Liu
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.|Center of Reproductive Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People's Republic of China.
Haiyan
H
Zheng
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Pingping
P
Guo
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Shuxian
S
Feng
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Xingyu
X
Zhou
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Desheng
D
Ye
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Xin
X
Chen
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China. chensl_92@163.com.
Shiling
S
Chen
D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human
Assisted reproductive technology; DNA methylation; DNA-methyltransferase; Single-nucleotide polymorphisms; Spontaneous abortion