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A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era.
PLoS One 2014; 9(10):e110093Plos

Abstract

BACKGROUND

Studies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk.

METHODS

The study included 457 US women diagnosed with either CIN 2+ (cases) or ≤ CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN.

RESULTS

The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017).

CONCLUSIONS

This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation.

Authors+Show Affiliations

The Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.Biosciences Division, Center for Cancer and Metabolism, SRI International, Menlo Park, California, United States of America.The Department of Pediatrics, Division of Biostatistics and Epidemiology, The University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.The Department of Community Health Outcomes and System, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.The Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.The Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.The Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25302494

Citation

Badiga, Suguna, et al. "A Lower Degree of PBMC L1 Methylation in Women With Lower Folate Status May Explain the MTHFR C677T Polymorphism Associated Higher Risk of CIN in the US Post Folic Acid Fortification Era." PloS One, vol. 9, no. 10, 2014, pp. e110093.
Badiga S, Johanning GL, Macaluso M, et al. A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era. PLoS ONE. 2014;9(10):e110093.
Badiga, S., Johanning, G. L., Macaluso, M., Azuero, A., Chambers, M. M., Siddiqui, N. R., & Piyathilake, C. J. (2014). A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era. PloS One, 9(10), pp. e110093. doi:10.1371/journal.pone.0110093.
Badiga S, et al. A Lower Degree of PBMC L1 Methylation in Women With Lower Folate Status May Explain the MTHFR C677T Polymorphism Associated Higher Risk of CIN in the US Post Folic Acid Fortification Era. PLoS ONE. 2014;9(10):e110093. PubMed PMID: 25302494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era. AU - Badiga,Suguna, AU - Johanning,Gary L, AU - Macaluso,Maurizio, AU - Azuero,Andres, AU - Chambers,Michelle M, AU - Siddiqui,Nuzhat R, AU - Piyathilake,Chandrika J, Y1 - 2014/10/10/ PY - 2014/06/17/received PY - 2014/09/15/accepted PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/12/19/medline SP - e110093 EP - e110093 JF - PloS one JO - PLoS ONE VL - 9 IS - 10 N2 - BACKGROUND: Studies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk. METHODS: The study included 457 US women diagnosed with either CIN 2+ (cases) or ≤ CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN. RESULTS: The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017). CONCLUSIONS: This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25302494/full_citation L2 - http://dx.plos.org/10.1371/journal.pone.0110093 DB - PRIME DP - Unbound Medicine ER -