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Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population

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Abstract

Background

Globally, congenital heart defect (CHD) is the most common congenital malformation, responsible for higher morbidity and mortality in the pediatric population. It is a complex multifactorial disease influenced by gene-environment and gene-gene interactions. The current study was the first attempt to study these polymorphisms in common clinical phenotypes of CHD in Pakistan and the association between maternal hypertension and diabetes with single nucleotide polymorphisms (SNPs) in children.

Methods

A total of 376 subjects were recruited in this current case-control study. Six variants from three genes were analyzed by cost-effective multiplex PCR and genotyped by minisequencing. Statistical analysis was done by GraphPad prism and Haploview. The association of SNPs and CHD was determined using logistic regression.

Results

The risk allele frequency was higher in cases as compared to healthy subjects, but the results were not significant for rs703752. However, stratification analysis suggested that rs703752 was significantly associated with the tetralogy of Fallot. The rs2295418 was significantly associated with maternal hypertension (OR = 16.41, p = 0.003), while a weak association was present between maternal diabetes and rs360057 (p = 0.08).

Conclusion

In conclusion, variants in transcriptional and signaling genes were associated with Pakistani pediatric CHD patients that showed varied susceptibility between different clinical phenotypes of CHD. In addition, this study was the first report regarding the significant association between maternal hypertension and the LEFTY2 gene variant.

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Data Availability

The datasets for this manuscript are not publicly available because it is a part of the PhD research work of Ms. Sana Ashiq. Requests to access the datasets should be directed to Sana Ashiq, email sanaashiq72@gmail.com.

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Acknowledgements

We would like to acknowledge CAMB, University of the Punjab for their kind support. We would also like to acknowledge hospital staff, patients, and their families for providing data.

Funding

Not Applicable.

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Authors and Affiliations

  1. Centre for Applied Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Thokar Niaz Baig, Lahore, 53700, Pakistan

    Sana Ashiq & Muhammad Farooq Sabar

Authors
  1. Sana Ashiq
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  2. Muhammad Farooq Sabar
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Contributions

SA conceptualized and designed the study, performed experiments, data collection, and analysis, and wrote, drafted, and proofread the manuscript. MFS supervised the study, designed the study, analyzed, drafted, and proofread the manuscript. All authors have read, approved, and agreed to be accountable for each aspect of the final draft of the manuscript.

Corresponding author

Correspondence to Muhammad Farooq Sabar.

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Consent to participate

Informed consent was obtained from the parents of study subjects.

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The authors declare that they have no conflicts of interest.

Ethics approval

This study was approved by the ethical committee of Children’s Hospital and The Institute of Child Health, Lahore (2021-282-CHICH) (2) Institutional Review Board Committee of Punjab University (84/DFEMS).

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Ashiq, S., Sabar, M.F. Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population. Mol Biol Rep 50, 5013–5020 (2023). https://doi.org/10.1007/s11033-023-08418-0

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  • DOI: https://doi.org/10.1007/s11033-023-08418-0

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