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The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population

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Abstract

Conotruncal heart defects (CTHDS) are a subgroup of congenital heart malformations that are considered to be a folate-sensitive birth defect. It has been hypothesized that polymorphisms in genes that code for key enzymes in the folate pathway may alter enzyme activity, leading to disruptions in folate metabolism and thus may influence the risk of such heart defects. This study was designed to investigate the association of six selected folate-metabolizing gene polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This was a case–control study involving 96 cases of CTHDs and 100 control samples, ranging in age from birth to 18 years. Genotyping using Sanger sequencing was performed for six single nucleotide polymorphisms of genes involved in folate metabolism. Logistic regression analyses revealed that for the 5,10-methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote genotype was associated with a significantly increased risk of CTHDs. The results of this study support an association between the inherited MTHFR A1298C genotype and the risk of CTHDs in an Indian population.

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Abbreviations

CTHDS:

Conotruncal heart defects

SNP:

Single nucleotide polymorphisms

MTHFR :

5,10-Methylenetetrahydrofolate reductase

CHD:

Congenital heart disease

TOF:

Tetralogy of Fallot

DORV:

Double outlet right ventricle

PA-VSD:

Pulmonary atresia with ventricular septal defect

TA:

Truncus arteriosus

IAA:

Interrupted aortic arch

DGS:

DiGeorge syndrome

VCFS:

Velocardiofacial

CAFS:

Conotruncal and facial anomaly

MTR :

Methionine synthase

MTRR :

Methionine synthase reductase

VSD:

Ventricular septal defect

ASD:

Atrioventricular septal defect

PS:

Pulmonary stenosis

CoA:

Coarctation of the aorta

HWE:

Hardy–Weinberg equilibrium

DNA:

Deoxyribonucleic acid

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Acknowledgments

The authors are grateful to all the study subjects and their parents for graciously volunteering for the study. We are indebted to Dr Kalpana Gowrishankar for her clinical inputs. We thank Ms. Shruthi Mohan, Ms. PriyankaV, Ms. Ganga Baskar and Ms. Raheema Beevi and Ms. Mohanapriya C.D for their assistance.

Conflict of interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, 600116, India

    Teena Koshy, Vettriselvi Venkatesan, Venkatachalam Perumal & Solomon Franklin Durairaj Paul

  2. Department of Medical Genetics, Manipal Hospital, Airport Road, Bengaluru, 560017, Karnataka, India

    Sridevi Hegde

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  1. Teena Koshy
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  2. Vettriselvi Venkatesan
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  3. Venkatachalam Perumal
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Correspondence to Solomon Franklin Durairaj Paul.

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Koshy, T., Venkatesan, V., Perumal, V. et al. The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population. Pediatr Cardiol 36, 1470–1475 (2015). https://doi.org/10.1007/s00246-015-1188-3

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  • DOI: https://doi.org/10.1007/s00246-015-1188-3

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