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Thymidylate synthase gene variation is associated with the risk for conotruncal heart defects in Chinese population

Published online by Cambridge University Press:  21 December 2018

Xike Wang ,
Haitao Wei ,
Yue Wu ,
Ying Tian  and
Lei Luo Open the ORCID record for Lei Luo [Opens in a new window]
Xike Wang
Affiliation:
Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang, China
Haitao Wei
Affiliation:
Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang, China
Yue Wu
Affiliation:
Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang, China
Ying Tian*
Affiliation:
Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang, China
Lei Luo*
Affiliation:
Department of Science and Education, Guizhou Provincial People’s Hospital, Guiyang, China
*
Author for correspondence: Lei Luo, Department of Science and Education, Guizhou Provincial People’s Hospital, Guiyang 550002, China. Tel: +86-0851-85273958; Fax: +86-0851-85273958; E-mail: linzhongyueliang@163.com; Ying Tian, Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang 550002, China. Tel: +86-0851-85273958; Fax: +86-0851-85273958; E-mail: 100877611@qq.com
Author for correspondence: Lei Luo, Department of Science and Education, Guizhou Provincial People’s Hospital, Guiyang 550002, China. Tel: +86-0851-85273958; Fax: +86-0851-85273958; E-mail: linzhongyueliang@163.com; Ying Tian, Department of Paediatrics, Guizhou Provincial People’s Hospital, Guiyang 550002, China. Tel: +86-0851-85273958; Fax: +86-0851-85273958; E-mail: 100877611@qq.com
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Abstract

Conotruncal heart defects are considered to be one of the most common types of birth defect worldwide. Genetic disturbances in folate metabolism such as Thymidylate synthase may increase risk for conotruncal heart defects. We evaluated two common Thymidylate synthase polymorphisms, including the 28 bp tandem repeat in the promoter enhancer region of the 5′-untranslated region and the 6 bp deletion in the 3′-untranslated region, as risk factors of conotruncal heart defects including various subtypes of malformations, in a total of 193 mothers with conotruncal heart defect in offspring and 234 healthy controls in the Chinese population. Logistic regression analyses revealed that mothers who were homozygotes with deletion (−/−) had a 1.8-fold (odds ratio: 1.8; 95% confidence interval: 1.0–3.0, p = 0.040) increased risk for conotruncal heart defect in offspring, respectively, when compared with mothers carrying the wild type (+/+) genotype. Consistently, individuals carrying the genotype −/− of the Thymidylate synthase 6 bp deletion also had higher plasma homocysteine levels compared to the mothers carrying the genotype +/+ in the control and conotruncal heart defect groups (p = 0.006 and p = 0.004, respectively). However, our results showed that Thymidylate synthase 28 bp tandem repeat polymorphism was not associated with risk for conotruncal heart defect and plasma homocysteine level. In conclusion, our data suggest that the maternal Thymidylate synthase 6 bp deletion polymorphism might be associated with plasma homocysteine level and risk for conotruncal heart defect in offspring.

Keywords

Conotruncal heart defectCHDThymidylate synthasefolatehomocysteine
Type
Original Article
Information
Cardiology in the Young , Volume 29 , Issue 3 , March 2019 , pp. 280 - 285
Copyright
© Cambridge University Press 2018. 

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Footnotes

*

These authors contributed equally to this work.

Cite this article: Wang X, Wei H, Wu Y, Tian Y, Luo L. (2019) Thymidylate synthase gene variation is associated with the risk for conotruncal heart defects in Chinese population. Cardiology in the Young29: 280–285. doi: 10.1017/S1047951118002184

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