TY - JOUR
T1 - Integration of methylation quantitative trait loci (mQTL) on dietary intake on DNA methylation levels
T2 - an example of n-3 PUFA and ABCA1 gene
AU - Fujii, Ryosuke
AU - Ando, Yoshitaka
AU - Yamada, Hiroya
AU - Tsuboi, Yoshiki
AU - Munetsuna, Eiji
AU - Yamazaki, Mirai
AU - Mizuno, Genki
AU - Maeda, Keisuke
AU - Ohashi, Koji
AU - Ishikawa, Hiroaki
AU - Watanabe, Mami
AU - Imaeda, Nahomi
AU - Goto, Chiho
AU - Wakai, Kenji
AU - Hashimoto, Shuji
AU - Suzuki, Koji
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/9
Y1 - 2023/9
N2 - Background: Epigenetic studies have reported relationships between dietary nutrient intake and methylation levels. However, genetic variants that may affect DNA methylation (DNAm) pattern, called methylation quantitative loci (mQTL), are usually overlooked in these analyses. We investigated whether mQTL change the relationship between dietary nutrient intake and leukocyte DNAm levels with an example of estimated fatty acid intake and ATP-binding cassette transporter A1 (ABCA1). Methods: A cross-sectional study on 231 participants (108 men, mean age: 62.7 y) without clinical history of cancer and no prescriptions for dyslipidemia. We measured leukocyte DNAm levels of 8 CpG sites within ABCA1 gene by pyrosequencing method and used mean methylation levels for statistical analysis. TaqMan assay was used for genotyping a genetic variant of ABCA1 (rs1800976). Dietary fatty acid intake was estimated with a validated food frequency questionnaire and adjusted for total energy intake by using residual methods. Results: Mean ABCA1 DNAm levels were 5% lower with the number of minor alleles in rs1800976 (CC, 40.6%; CG, 35.9%; GG, 30.6%). Higher dietary n-3 PUFA intake was associated with lower ABCA1 DNAm levels (1st (ref) vs. 4th, β [95% CI]: –2.52 [–4.77, –0.28]). After controlling for rs180076, the association between dietary n-3 PUFA intake and ABCA1 DNAm levels was attenuated, but still showed an independent association (1st (ref) vs. 4th, β [95% CI]: –2.00 [–3.84, –0.18]). The interaction of mQTL and dietary n-3 PUFA intake on DNAm levels was not significant. Conclusions: This result suggested that dietary n-3 PUFA intake would be an independent predictor of DNAm levels in ABCA1 gene after adjusting for individual genetic background. Considering mQTL need to broaden into other genes and nutrients for deeper understanding of DNA methylation, which can contribute to personalized nutritional intervention.
AB - Background: Epigenetic studies have reported relationships between dietary nutrient intake and methylation levels. However, genetic variants that may affect DNA methylation (DNAm) pattern, called methylation quantitative loci (mQTL), are usually overlooked in these analyses. We investigated whether mQTL change the relationship between dietary nutrient intake and leukocyte DNAm levels with an example of estimated fatty acid intake and ATP-binding cassette transporter A1 (ABCA1). Methods: A cross-sectional study on 231 participants (108 men, mean age: 62.7 y) without clinical history of cancer and no prescriptions for dyslipidemia. We measured leukocyte DNAm levels of 8 CpG sites within ABCA1 gene by pyrosequencing method and used mean methylation levels for statistical analysis. TaqMan assay was used for genotyping a genetic variant of ABCA1 (rs1800976). Dietary fatty acid intake was estimated with a validated food frequency questionnaire and adjusted for total energy intake by using residual methods. Results: Mean ABCA1 DNAm levels were 5% lower with the number of minor alleles in rs1800976 (CC, 40.6%; CG, 35.9%; GG, 30.6%). Higher dietary n-3 PUFA intake was associated with lower ABCA1 DNAm levels (1st (ref) vs. 4th, β [95% CI]: –2.52 [–4.77, –0.28]). After controlling for rs180076, the association between dietary n-3 PUFA intake and ABCA1 DNAm levels was attenuated, but still showed an independent association (1st (ref) vs. 4th, β [95% CI]: –2.00 [–3.84, –0.18]). The interaction of mQTL and dietary n-3 PUFA intake on DNAm levels was not significant. Conclusions: This result suggested that dietary n-3 PUFA intake would be an independent predictor of DNAm levels in ABCA1 gene after adjusting for individual genetic background. Considering mQTL need to broaden into other genes and nutrients for deeper understanding of DNA methylation, which can contribute to personalized nutritional intervention.
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U2 - 10.1038/s41430-023-01315-6
DO - 10.1038/s41430-023-01315-6
M3 - Article
C2 - 37542202
AN - SCOPUS:85166644544
SN - 0954-3007
VL - 77
SP - 881
EP - 887
JO - European Journal of Clinical Nutrition
JF - European Journal of Clinical Nutrition
IS - 9
ER -
