Associations between Two Genetic Variants in NKX2-5 and Risk of Congenital Heart Disease in Chinese Population: A Meta-Analysis

Wang, Zhenling; Zou, Li; Zhong, Rong; Zhu, Beibei; Chen, Wei; Shen, Na; Ke, Juntao; Lou, Jiao; Song, Ranran; Miao, Xiaoping

doi:10.1371/journal.pone.0070979

Cited by 12 publications

(8 citation statements)

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“…Seven studies were included in a meta-analysis of the association between NKX2-5 63A>G and congenital heart disease in the Chinese population, which showed a pooled OR of 1.26 (95% CI, 1.02–1.56). 69 Four studies included in meta-analysis showed no evidence for association between NKX2-5 60G>C and CHD.…”

Section: Resultsmentioning

confidence: 95%

“…NKX2-5 and GATA4 are cardiac transcription factors that regulate heart development. 69 NKX2-5 has been shown to participate in heart development not only in animal models, such as zebrafish, frog, chicken, and mouse, but also in humans in previous family studies. 69 During the first trimester of gestation, male external genitalia are developed by regulation of androgens, such as testosterone and dihydrotestosterone.…”

Section: Discussionmentioning

confidence: 99%

“… 69 NKX2-5 has been shown to participate in heart development not only in animal models, such as zebrafish, frog, chicken, and mouse, but also in humans in previous family studies. 69 During the first trimester of gestation, male external genitalia are developed by regulation of androgens, such as testosterone and dihydrotestosterone. Since SRD5A2 plays a role in androgen synthesis and metabolism, it may have an effect on the differentiation of genitalia in males.…”

Section: Discussionmentioning

confidence: 99%

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Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

et al. 2021

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Background The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. Methods We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. Results We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR , MTRR and MTR , GATA4 , NKX2-5 , SRD5A2 , CFTR, and 1p22 and 20q12 anomalies. Conclusion This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

et al. 2021

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“…The rs2277923 is a synonymous variant in which arginine is replaced by guanine at position 63 on exon 1. This polymorphism affects the normal gene function that was first reported in 52 control subjects by Benson et al in 199 [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

Ashiq

Sabar

2021

Egypt Heart J

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Background The gene NKX2-5 is a key transcription factor that plays an essential role in normal cardiac development. Although some recent studies have studied the role of polymorphisms in the NKX2-5 gene in congenital heart diseases (CHDs), the results were not consistent and remained uncertain. Therefore, we conduct a review of literature and investigate the association of genetic polymorphisms with CHDs. Results We selected seventeen studies regarding the association of NKX2-5 gene rs2277923 polymorphism with CHDs. Overall, in all the tested genetic models, the 63A > G polymorphism was not significantly associated with increased congenital heart defects risk. We used pooled odds ratios (OR) to calculate the association of CHDs with rs2277923 including allelic model: OR 1.00, 95% CI 0.82–1.21; homozygote model: OR 0.95, 95%CI 0.68–1.33, recessive model: OR 0.89 CI 0.70–1.13, heterozygote model: OR: 1.09, 95%CI 0.87–1.37, dominant model: OR 1.08 CI 0.82–1.42 and overdominant model: OR 1.17 CI 1.01–1.35. In addition, our analysis suggests that no publication bias exists in this meta-analysis. Conclusions Our findings suggested that 63A > G polymorphism in the NKX2-5 gene was not significantly associated with congenital heart defects. However, in the future, more studies with increased sample size are required that may provide us more definite conclusions.

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“…The NKX2-5 is a member of the NKX2 family located on chromosome 5134 and consists of two exons that encode a 324-amino acid transcription factor. The genetic polymorphism rs2277923 is a synonymous mutation 63A>G leading to an amino acid substitution of glutamine by glutamine at position 21 (Glu21Glu) and was reported as a genetic predictor of CHD [ 7 ]. In addition, GATA4 interacts with NKX2-5 , and it is known that mutations in transcription factors can result in severe cardiac defects [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Association of NFKB1, NKX2-5, GATA4 and RANKL gene polymorphisms with sporadic congenital heart disease in Greek patients

Aidinidou

Chatzikyriakidou

Giannopoulos

et al. 2021

Balkan Journal of Medical Genetics

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Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the NFKB1 gene polymorphism (–94ins/ delATTG), rs28362491, NKX2-5 gene polymorphism rs2277923, GATA4 gene polymorphism rs11785481 and RANKL gene polymorphism rs4531631. A total of 43 CHD patients and 100 healthy adults were included in the study. The polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) method was used to genotype the aforementioned polymorphisms of NFKB1, NKX2-5, GATA4 and RANKL. The association analysis identified that there was a protective association between CHD and the A allele of rs2277923 polymorphism (p = 0.004). The D allele of the rs28362491 polymorphism is also a likely risk factor for causing CHD (p = 0.006). The differences of the rs4531631 and rs11785481 variant contribution had no statistical significance between the groups (p >0.05). In conclusion, our results revealed that the rs28362491 and rs2277923 gene polymorphisms, but not the rs4531631 and rs11785481 polymorphisms, may contribute to CHD risk in a cohort of Greek CHD patients.

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Associations between Two Genetic Variants in NKX2-5 and Risk of Congenital Heart Disease in Chinese Population: A Meta-Analysis

Cited by 12 publications

References 44 publications

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

Association of NFKB1, NKX2-5, GATA4 and RANKL gene polymorphisms with sporadic congenital heart disease in Greek patients

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