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Published on: May 10, 2024
Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status
Chandrika J Piyathilake1, Maria Azrad, Maurizio Macaluso
1University of Alabama at Birmingham, Birmingham, Alabama, USA. piyathic@uab.edu
Objectives:
We previously reported that women polymorphic for the methylenetetrahydrofolate reductase (MTHFR) gene were less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3 (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.21-0.78, P = 0.007). In the present study, we tested whether this protective association is modified by circulating riboflavin status in the same study population.
Methods:
Riboflavin status was assessed by the erythrocyte glutathione reductase assay and expressed in terms of an erythrocyte glutathione reductase activity coefficient. The status of MTHFR polymorphism, riboflavin, and circulating concentrations of folate, vitamins B12, A, E, and C, and total carotene were ascertained in 170 White and 265 African-American women positive for the cervical presence of high-risk human papilloma virus. Presence/absence of CIN 2 or 3 was determined histologically, and associations with risk factors were examined using multiple logistic regression. Eighty women with CIN 2 or 3 lesions were compared with 355 women without cervical lesions. Based on the median erythrocyte glutathione reductase activity coefficient of 1.4, women were grouped into low (>1.4) and high (< or =1.4) riboflavin status.
Results:
Women with MTHFR polymorphism and low riboflavin status were significantly less likely to have CIN 2 or 3 than was the referent group of women without the polymorphism and high riboflavin status (OR 0.35, 95% CI 0.13-0.92, P = 0.034). MTHFR polymorphism was not associated with CIN 2 or 3 in women with high riboflavin status (OR 0.51, 95% CI 0.22-1.19, P = 0.119), nor were any of the associations influenced by folate levels.
Conclusion:
A further inactivation of polymorphic MTHFR by low riboflavin status and a resulting shift in the folate metabolic pathway toward DNA synthesis may explain these observations. The practical implications of this complex gene-nutrient-disease interaction will require further investigation.
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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
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