Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study

Background. Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with...

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Main Authors: Mingyi Zhao, Jingyi Diao, Peng Huang, Jinqi Li, Yihuan Li, Yang Yang, Liu Luo, Senmao Zhang, Letao Chen, Tingting Wang, Ping Zhu, Jiabi Qin
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2020/3854630
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author Mingyi Zhao
Jingyi Diao
Peng Huang
Jinqi Li
Yihuan Li
Yang Yang
Liu Luo
Senmao Zhang
Letao Chen
Tingting Wang
Ping Zhu
Jiabi Qin
author_facet Mingyi Zhao
Jingyi Diao
Peng Huang
Jinqi Li
Yihuan Li
Yang Yang
Liu Luo
Senmao Zhang
Letao Chen
Tingting Wang
Ping Zhu
Jiabi Qin
author_sort Mingyi Zhao
collection DOAJ
description Background. Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with diabetes mellitus (DM) and single nucleotide polymorphisms (SNPs) of NKX2.5. Methods and Results. A case-control study of 620 mothers of CHD patients and 620 mothers of healthy children admitted to Hunan Children’s Hospital from November 2017 to December 2019 was conducted. We collected the mothers’ information by questionnaire and detected children’s NKX2.5 variants with a MassARRAY system. The interaction coefficient (γ) was used to quantify the estimated gene-environment interactions. Univariate and multivariate analyses both showed that the infants had a higher risk of CHD if their mothers had a history of DM, including gestational DM (GDM) during this pregnancy (adjusted odds ratio [aOR=4.98]), GDM in previous pregnancies (aOR=4.30), and pregestational DM (PGDM) in the 3 months before this pregnancy (aOR=6.78). Polymorphisms of the NKX2.5 gene at rs11802669 (C/C vs. T/T: aOR=4.97; C/T vs. T/T: aOR=2.15) and rs2277923 (T/T vs. C/C, aOR=1.74; T/C vs. C/C, aOR=1.61) were significantly associated with the risk of CHD in offspring. In addition, significant interactions between maternal DM and NKX2.5 genetic variants at rs11802669 (aOR=8.12) and rs2277923 (aOR=17.72) affecting the development of CHD were found. Conclusions. These results suggest that maternal DM, NKX2.5 genetic variants, and their interactions are significantly associated with the risk of CHD in offspring.
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spelling doaj-art-56e1e6b0bb9c4471b422596edce2e4992025-02-03T06:45:47ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/38546303854630Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control StudyMingyi Zhao0Jingyi Diao1Peng Huang2Jinqi Li3Yihuan Li4Yang Yang5Liu Luo6Senmao Zhang7Letao Chen8Tingting Wang9Ping Zhu10Jiabi Qin11Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Cardiothoracic Surgery, Hunan Children’s Hospital, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaGuangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, ChinaBackground. Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with diabetes mellitus (DM) and single nucleotide polymorphisms (SNPs) of NKX2.5. Methods and Results. A case-control study of 620 mothers of CHD patients and 620 mothers of healthy children admitted to Hunan Children’s Hospital from November 2017 to December 2019 was conducted. We collected the mothers’ information by questionnaire and detected children’s NKX2.5 variants with a MassARRAY system. The interaction coefficient (γ) was used to quantify the estimated gene-environment interactions. Univariate and multivariate analyses both showed that the infants had a higher risk of CHD if their mothers had a history of DM, including gestational DM (GDM) during this pregnancy (adjusted odds ratio [aOR=4.98]), GDM in previous pregnancies (aOR=4.30), and pregestational DM (PGDM) in the 3 months before this pregnancy (aOR=6.78). Polymorphisms of the NKX2.5 gene at rs11802669 (C/C vs. T/T: aOR=4.97; C/T vs. T/T: aOR=2.15) and rs2277923 (T/T vs. C/C, aOR=1.74; T/C vs. C/C, aOR=1.61) were significantly associated with the risk of CHD in offspring. In addition, significant interactions between maternal DM and NKX2.5 genetic variants at rs11802669 (aOR=8.12) and rs2277923 (aOR=17.72) affecting the development of CHD were found. Conclusions. These results suggest that maternal DM, NKX2.5 genetic variants, and their interactions are significantly associated with the risk of CHD in offspring.http://dx.doi.org/10.1155/2020/3854630
spellingShingle Mingyi Zhao
Jingyi Diao
Peng Huang
Jinqi Li
Yihuan Li
Yang Yang
Liu Luo
Senmao Zhang
Letao Chen
Tingting Wang
Ping Zhu
Jiabi Qin
Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
Journal of Diabetes Research
title Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
title_full Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
title_fullStr Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
title_full_unstemmed Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
title_short Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study
title_sort association of maternal diabetes mellitus and polymorphisms of the nkx2 5 gene in children with congenital heart disease a single centre based case control study
url http://dx.doi.org/10.1155/2020/3854630
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