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Maternal one-carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India.

Abstract

BACKGROUND

Neural tube defects (NTDs) are among the most common severe congenital malformations, representing a long-term public health burden in India. A deranged one-carbon metabolism and genes regulating this metabolism have been linked to NTDs. Vitamin B(12) deficiency is reported to be more prevalent than folate deficiency in the Indian population. We investigated the role of maternal nutritional and genetic markers related to one-carbon metabolism in the etiology of NTDs.

METHODS

We conducted a multicenter case-control study to compare plasma folate, vitamin B(12) , homocysteine and holo-transcobalamin levels, and polymorphisms in methylenetetrahydrofolate reductase (MTHFR, 677C>T, 1298A>C, 1781G>A and 236+724A>G) and transcobalamin (TCN2, 776C>G) genes, in 318 women with NTD-affected offspring (cases) and 702 women with apparently healthy offspring (controls). The samples were collected at diagnosis in cases and at delivery in controls.

RESULTS

We observed a significant association of high maternal plasma homocysteine concentrations with NTDs in the offspring (p = 0.026). There was no association of maternal folate or B(12) levels with NTDs (p > 0.05) but low maternal holo-transcobalamin predicted strong risk of NTDs in the offspring (p = 0.003). The commonly associated maternal polymorphism 677C>T in the MTHFR gene did not predict risk of NTDs in the offspring (p > 0.05) and 1298A>C and 1781G>A polymorphisms in MTHFR were protective (p = 0.024 and 0.0004 respectively). Maternal 776C>G polymorphism in TCN2 was strongly predictive of NTD in the offspring (p = 0.006).

CONCLUSION

Our study has demonstrated a possible role for maternal B(12) deficiency in the etiology of NTDs in India over and above the well-established role of folate deficiency.

Authors+Show Affiliations

Diabetes Unit, KEM Hospital Research Center, Rasta Peth, Pune, India.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21770021

Citation

Godbole, Koumudi, et al. "Maternal One-carbon Metabolism, MTHFR and TCN2 Genotypes and Neural Tube Defects in India." Birth Defects Research. Part A, Clinical and Molecular Teratology, vol. 91, no. 9, 2011, pp. 848-56.
Godbole K, Gayathri P, Ghule S, et al. Maternal one-carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India. Birth Defects Res Part A Clin Mol Teratol. 2011;91(9):848-56.
Godbole, K., Gayathri, P., Ghule, S., Sasirekha, B. V., Kanitkar-Damle, A., Memane, N., ... Yajnik, C. S. (2011). Maternal one-carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India. Birth Defects Research. Part A, Clinical and Molecular Teratology, 91(9), pp. 848-56. doi:10.1002/bdra.20841.
Godbole K, et al. Maternal One-carbon Metabolism, MTHFR and TCN2 Genotypes and Neural Tube Defects in India. Birth Defects Res Part A Clin Mol Teratol. 2011;91(9):848-56. PubMed PMID: 21770021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maternal one-carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India. AU - Godbole,Koumudi, AU - Gayathri,Panjalingam, AU - Ghule,Smita, AU - Sasirekha,Batchu Venkatanaga, AU - Kanitkar-Damle,Amruta, AU - Memane,Nilam, AU - Suresh,Seshadri, AU - Sheth,Jayesh, AU - Chandak,Giriraj Ratan, AU - Yajnik,Chittaranjan S, Y1 - 2011/07/18/ PY - 2010/11/29/received PY - 2011/04/28/revised PY - 2011/05/07/accepted PY - 2011/7/20/entrez PY - 2011/7/20/pubmed PY - 2011/12/31/medline SP - 848 EP - 56 JF - Birth defects research. Part A, Clinical and molecular teratology JO - Birth Defects Res. Part A Clin. Mol. Teratol. VL - 91 IS - 9 N2 - BACKGROUND: Neural tube defects (NTDs) are among the most common severe congenital malformations, representing a long-term public health burden in India. A deranged one-carbon metabolism and genes regulating this metabolism have been linked to NTDs. Vitamin B(12) deficiency is reported to be more prevalent than folate deficiency in the Indian population. We investigated the role of maternal nutritional and genetic markers related to one-carbon metabolism in the etiology of NTDs. METHODS: We conducted a multicenter case-control study to compare plasma folate, vitamin B(12) , homocysteine and holo-transcobalamin levels, and polymorphisms in methylenetetrahydrofolate reductase (MTHFR, 677C>T, 1298A>C, 1781G>A and 236+724A>G) and transcobalamin (TCN2, 776C>G) genes, in 318 women with NTD-affected offspring (cases) and 702 women with apparently healthy offspring (controls). The samples were collected at diagnosis in cases and at delivery in controls. RESULTS: We observed a significant association of high maternal plasma homocysteine concentrations with NTDs in the offspring (p = 0.026). There was no association of maternal folate or B(12) levels with NTDs (p > 0.05) but low maternal holo-transcobalamin predicted strong risk of NTDs in the offspring (p = 0.003). The commonly associated maternal polymorphism 677C>T in the MTHFR gene did not predict risk of NTDs in the offspring (p > 0.05) and 1298A>C and 1781G>A polymorphisms in MTHFR were protective (p = 0.024 and 0.0004 respectively). Maternal 776C>G polymorphism in TCN2 was strongly predictive of NTD in the offspring (p = 0.006). CONCLUSION: Our study has demonstrated a possible role for maternal B(12) deficiency in the etiology of NTDs in India over and above the well-established role of folate deficiency. SN - 1542-0760 UR - https://www.unboundmedicine.com/medline/citation/21770021/Maternal_one_carbon_metabolism_MTHFR_and_TCN2_genotypes_and_neural_tube_defects_in_India_ L2 - https://doi.org/10.1002/bdra.20841 DB - PRIME DP - Unbound Medicine ER -