AUTHOR=Stojković Ljiljana , Zec Manja , Zivkovic Maja , Bundalo Maja , Bošković Maja , Glibetić Marija , Stankovic Aleksandra 

TITLE=Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

JOURNAL=Frontiers in Nutrition

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.689055

DOI=10.3389/fnut.2021.689055

ISSN=2296-861X

ABSTRACT=<p>Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov</ext-link>) aimed to determine the impact of 4-week daily consumption of polyphenol-rich <italic>Aronia melanocarpa</italic> juice (AMJ) treatment on <italic>Long Interspersed Nucleotide Element-1</italic> (<italic>LINE-1</italic>) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (<italic>n</italic> = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, <italic>MTHFR</italic> C677T gene variant, anthropometric and metabolic parameters) modulated the <italic>LINE-1</italic> methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of <italic>LINE-1</italic> methylation was done by MethyLight method. <italic>MTHFR</italic> C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (<italic>n</italic> = 22), we observed significant decreases in <italic>LINE-1</italic> methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; <italic>P</italic> = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; <italic>P</italic> = 0.02]. The change (after vs. before treatment) in <italic>LINE-1</italic> methylation directly correlated with the presence of <italic>MTHFR</italic> 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (<italic>R</italic> = 0.72, <italic>R</italic><sup>2</sup> = 0.52, adjusted <italic>R</italic><sup>2</sup> = 0.36, <italic>P</italic> = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.</p>