TY - JOUR
T1 - Folate deficiency is not associated with increased mitochondrial genomic instability
T2 - Results from dietary intake and lymphocytic mtDNA 4977-bp deletion in healthy young women in Italy
AU - Agodi, Antonella
AU - Barchitta, Martina
AU - Quattrocchi, Annalisa
AU - Marchese, Anna Elisa
AU - Boffetta, Paolo
N1 - Funding Information:
This work was supported in part by grants from the University of Catania (Progetti di Ricerca di Ateneo to A.A.).
PY - 2014/3
Y1 - 2014/3
N2 - The mitochondrial DNA (mtDNA) 4977-bp deletion is a biomarker of mitochondrial genomic instability. It is frequently detected in a number of sporadic diseases, and it accumulates in many tissues during aging. Folic acid plays an important role in the maintenance of genomic stability in mammals. The aim of the present cross-sectional study was to characterise the levels of the mtDNA deletion in the lymphocytes of healthy young women, taking into account folate intake, red blood cell (RBC) folate levels and the distribution of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism. Folate intake was estimated by a food frequency questionnaire. Determination of the MTHFR C677T polymorphism and of the mtDNA deletion was performed by real-time polymerase chain reaction analysis. A total of 476 women were enrolled. Low levels of deletion were found (mean ΔCt = 1.24). After multivariate analysis, results did not show any significant relationship between age, smoking habits, pregnancy status, nutritional status, inadequate folate intake, folate deficiency, use of folic acid supplements, MTHFR C677T polymorphism and mtDNA 4977-bp deletions. The lack of association between inadequate folate intake, folate deficiency and mitochondrial genomic instability was confirmed also considering reference values of folate based on DNA damage prevention. Our results indicate that mtDNA 4977-bp deletions are maintained at low levels in lymphocytes of young healthy women despite the wide range of variation of folate intakes and folate status. Future studies, carefully designed to address limits and methodological issues related to variation of this biomarker as an effect of different dietary patterns and of folate status, could provide further insight on the specific mechanisms that are acting in lymphocytes of healthy subjects under observed folate intake.
AB - The mitochondrial DNA (mtDNA) 4977-bp deletion is a biomarker of mitochondrial genomic instability. It is frequently detected in a number of sporadic diseases, and it accumulates in many tissues during aging. Folic acid plays an important role in the maintenance of genomic stability in mammals. The aim of the present cross-sectional study was to characterise the levels of the mtDNA deletion in the lymphocytes of healthy young women, taking into account folate intake, red blood cell (RBC) folate levels and the distribution of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism. Folate intake was estimated by a food frequency questionnaire. Determination of the MTHFR C677T polymorphism and of the mtDNA deletion was performed by real-time polymerase chain reaction analysis. A total of 476 women were enrolled. Low levels of deletion were found (mean ΔCt = 1.24). After multivariate analysis, results did not show any significant relationship between age, smoking habits, pregnancy status, nutritional status, inadequate folate intake, folate deficiency, use of folic acid supplements, MTHFR C677T polymorphism and mtDNA 4977-bp deletions. The lack of association between inadequate folate intake, folate deficiency and mitochondrial genomic instability was confirmed also considering reference values of folate based on DNA damage prevention. Our results indicate that mtDNA 4977-bp deletions are maintained at low levels in lymphocytes of young healthy women despite the wide range of variation of folate intakes and folate status. Future studies, carefully designed to address limits and methodological issues related to variation of this biomarker as an effect of different dietary patterns and of folate status, could provide further insight on the specific mechanisms that are acting in lymphocytes of healthy subjects under observed folate intake.
UR - http://www.scopus.com/inward/record.url?scp=84894265560&partnerID=8YFLogxK
U2 - 10.1093/mutage/get065
DO - 10.1093/mutage/get065
M3 - Article
C2 - 24419225
AN - SCOPUS:84894265560
SN - 0267-8357
VL - 29
SP - 101
EP - 106
JO - Mutagenesis
JF - Mutagenesis
IS - 2
ER -