DNA methyltransferase 1 rs16999593 genetic polymorphism decreases risk in patients with transposition of great arteries.
Complete transposition of the great arteries (TGA) is the most frequent cyanotic heart defect diagnosed in neonates. However, the exact etiology of TGA is unknown. The aim of the present study was to assess the association of TGA pathogenesis with single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs)-1 and 3a- in Chinese children. We genotyped 5 SNPs (rs16999593, rs16999358, and rs2228611 in DNMT1; and rs2276599 and rs2276598 in DNMT3A) in 206 patients with complete TGA and 252 healthy children. Statistical analysis was performed to explore the association of the 5 SNPs with complete TGA susceptibility. Compared with the T/T and C/C genotypes, the heterozygous genotype C/T of rs16999593 correlated with a decreased risk for complete TGA under codominant (OR=0.46; 95% CI=0.29-0.72), dominant (OR=0.58; 95% CI=0.38-0.88), and overdominant (OR=0.44; 95% CI=0.28-0.68) models. In contrast, the genotype C/C of rs16999593 correlated with a higher risk for TGA under a recessive model (OR=3.15; 95% CI=1.14-8.68) compared with the T/T and C/T genotypes. Furthermore, the TGC, TGT, CGC, and CGT haplotypes of DNMT1 did not differ significantly between the two groups, whereas the frequency of the TAC haplotype was lower in the case group (OR<1; P=0.002). No significant differences in the frequencies of the TC, CC, TT, and CT haplotypes of DNMT3A were found between the two groups. Furthermore, logistic regression showed that sex and the rs16999358 SNP were two independent risk factors for complete TGA. Overall, the C/T genotype of the rs16999593 SNP in DNMT1 might decrease the risk of complete TGA pathogenesis in the Southern Chinese population.
Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou 510080, China.
Liming
L
Lei
Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Haoming
H
Lin
Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Shilong
S
Zhong
Department of Pediatrics of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Zhiwei
Z
Zhang
Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou 510080, China.
Jimei
J
Chen
Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Xiyong
X
Yu
Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou 510080, China.
Xiaoqing
X
Liu
Department of Pediatrics of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Cheng
C
Zhang
Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou 510080, China.
Zhiqiang
Z
Nie
Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou 510080, China. Electronic address: zhuangjian5413@tom.com.
Jian
J
Zhuang
D044466:Asian People; D016022:Case-Control Studies; D002648:Child; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014188:Transposition of Great Vessels / Q000235:genetics*
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
Complete transposition of the great arteries; DNA methylation; DNA methyltransferases; Gene polymorphisms; Real-time qPCR