Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with vitamin B12 deficiency and adverse perinatal outcomes among pregnant women of rural South India – a cross sectional longitudinal study

Anitha M. Barney; Sumita Danda; Anne G. Cherian; Jency Aronraj; Lavanya Jayaprakash; Vinod J. Abraham; Christhunesa S. Christudass; Tobey A. Marcus

doi:10.1515/jpm-2022-0119

Article

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with vitamin B12 deficiency and adverse perinatal outcomes among pregnant women of rural South India – a cross sectional longitudinal study

Anitha M. Barney , Sumita Danda , Anne G. Cherian , Jency Aronraj , Lavanya Jayaprakash , Vinod J. Abraham , Christhunesa S. Christudass and Tobey A. Marcus

Published/Copyright: July 11, 2022

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From the journal Journal of Perinatal Medicine Volume 50 Issue 9

Abstract

Objectives

To determine the occurrence of MTHFR gene polymorphisms and to study their association with vitamin B12 deficiency and adverse perinatal outcomes among a cohort of pregnant women from Kaniyambadi block, Tamil Nadu.

Methods

120 consecutive pregnant women who were ≤20 weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed.

Results

Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (χ²)=7.9 and 7.6 respectively; p=0.02]. Heterozygous pathogenic variant c.1262G>T was associated with both adverse maternal [χ²=11.5; p=0.001] and neonatal [χ²=18.3; p=0.009] outcomes.

Conclusions

MTHFR gene polymorphisms could be associated with several adverse perinatal outcomes and vitamin B12 deficiency. Further larger studies are needed to prove the pathogenicity of c.1262G>T variant on pregnancy.

Keywords: maternal adverse outcome; MTHFR A1298C; MTHFR C677T; MTHFR G1262T; neonatal adverse outcome

Corresponding author: Anitha Mohanraj Barney, Department of Clinical Genetics, Christian Medical College, Ida Scudder Road-632004, Vellore, Tamil Nadu, India, Phone: 0416 2283161, E-mail: anithabarney@cmcvellore.ac.in

Funding source: Fluid research grant, Institutional Review Board (IRB), Christian Medical College, Vellore

Award Identifier / Grant number: 11813

Award Identifier / Grant number: Unassigned

Acknowledgments

We acknowledge the Institutional Review Board (IRB), Christian Medical College, Vellore for providing fluid research grant to carry out this research.

Research funding: Fluid research grant, Institutional Review Board (IRB), Christian Medical College, Vellore, Tamil Nadu, India.
Author contributions: Anitha Mohanraj Barney, Sumita Danda, Anne George Cherian and Vinod Joseph Abraham designed the study. All authors had helped in the laboratory analysis, the interpretation and conclusion of the results. Anitha Mohanraj Barney collected the data, analysed and prepared the manuscript; the manuscript was critically reviewed by all the authors. The final version was approved by all the authors and all the authors take responsibility for all the aspects of the research work.
Competing interests: Authors have no conflict of interest to declare.
Informed consent: Informed consent was obtained from all the participants, and all the necessary follow up details were extracted from the electronic database.
Ethical approval: This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. This study was approved by Institutional Review Board of Christian Medical College, Vellore, Tamil Nadu, India.

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Received: 2022-03-02

Accepted: 2022-06-11

Published Online: 2022-07-11

Published in Print: 2022-11-25

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Articles in the same Issue

https://doi.org/10.1515/jpm-2022-0119

Keywords for this article

maternal adverse outcome; MTHFR A1298C; MTHFR C677T; MTHFR G1262T; neonatal adverse outcome