A Lower Degree of PBMC Li 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

作者：Badiga Suguna; Johanning Gary L; Macaluso Maurizio; Azuero Andres; Chambers Michelle M; Siddiqui Nuzhat R; Piyathilake Chandrika J^*

来源：PLos One, 2014, 9(10): e110093.

DOI：10.1371/journal.pone.0110093

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 IVITHFR 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 (Us), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk. %26lt;br%26gt;Methods: The study included 457 US women diagnosed with either CIN 2+ (cases) or %26lt; CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN. %26lt;br%26gt;Results: The 677CT11T 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 CTaT 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 Li methylation compared to women with CT/TT genotype with higher folate (OR =0.28, P =0.017). %26lt;br%26gt;Conclusions: This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC Li 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.

• 出版日期2014-10-10