From: Effect of epigenetics on vitamin D levels: a systematic review until December 2020
First author | Year of publication | Study type | Country /Ethnicity | Population-specific characteristics | Correlation between | Total number | Gene | CpG | CpG ID | Chromosome: position | Location type | Coefficient of determination (R2) | Correlation coefficient (r) | Beta coefficient (β) | FDR | P-value |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Wjst et al., (27) | 2010 | Cross-sectional | Germany | 25(OH)D3 level with methylation rate of CpG sites | 383 | CYP27B1 | CpG 15–17 b | 0.11 | All p-values < 0.05 | |||||||
O’Brien et al., (28) | 2018 | Case-cohort sample | USA/ Non-Hispanic white | All cases were women | 25(OH)D level and with methylation level of CpGs | 1270 | RXRA | cg21201924 | 9: 137,251,825 | Body | −0.02 a | < 0.001 | ||||
RXRA | cg02127980 | 9: 137,252,116 | Body | −0.015 a | < 0.001 | |||||||||||
NADSYN1 | cg17559402 | 11: 71,187,890 | Body | −0.02 a | 0.003 | |||||||||||
RXRA | cg02059519 | 9: 137,250,935 | Body | −0.01 a | 0.003 | |||||||||||
GC | cg09997530 | 4: 72,636,217 | Body | 0.02 a | 0.005 | |||||||||||
RXRA | cg04329455 | 9: 137,215,364 | 0.01 a | 0.007 | ||||||||||||
NADSYN1 | cg00268518 | 11: 71,164,106 | TSS200 | 0.01 a | 0.008 | |||||||||||
NADSYN1 | cg03146219 | 11: 71,189,514 | Body | −0.01 a | 0.009 | |||||||||||
RXRA | cg13510651 | 9: 137,227,772 | Body | −0.01 a | 0.01 | |||||||||||
DHCR7 | cg03490288 | 11: 71,146,658 | Body | 0.02 a | 0.01 | |||||||||||
NADSYN1 | cg05785753 | 11: 71,189,490 | Body | −0.01 a | 0.01 | |||||||||||
RXRA | cg13687497 | 9: 137,249,839 | Body | −0.01 a | 0.01 | |||||||||||
NADSYN1 | cg07793224 | 11: 71,183,180 | Body | 0.02 a | 0.02 | |||||||||||
DHCR7 | cg26044621 | 11: 71,145,665 | 3´ UTR | 0.01 a | 0.02 | |||||||||||
GC | cg04837494 | 4: 72,608,149 | 3´ UTR | 0.01 a | 0.03 | |||||||||||
RXRA | cg14236758 | 9: 137,252,129 | Body | −0.009 a | 0.03 | |||||||||||
NADSYN1 | cg04774822 | 11: 71,165,839 | Body | −0.009 a | 0.03 | |||||||||||
DHCR7 | cg16151558 | 11: 71,159,853 | TSS1500 | 0.01 a | 0.04 | |||||||||||
CYP27B1 | cg20372759 | 12: 58,162,287 | TSS1500 | −0.01 a | 0.04 | |||||||||||
GC | cg24806812 | 4: 72,635,202 | Body | 0.01 a | 0.04 | |||||||||||
RXRA | cg14154547 | 9: 137,293,309 | Body | −0.007 a | 0.04 | |||||||||||
DHCR7 | cg07099121 | 11: 71,146,096 | 3´ UTR | −0.01 a | 0.04 | |||||||||||
NADSYN1 | cg16910670 | 11: 71,215,361 | −0.01 a | 0.05 | ||||||||||||
Harvey et al., (31) | 2014 | Cohort | UK | Mothers and their newborns | Maternal free 25(OH)-vitamin D index (ratio of serum 25(OH)D to DBP concentrations) measured at 34 weeks gestation with cord RXRA percent methylation | 64 | RXRA | CpG 4/5 b | 9: 136355593,600 + | -3.29 | 0.03 | |||||
Novakovic et al., (30) | 2012 | Cohort | Australia | Mothers and their newborns | Maternal 25(OH)D concentrations (at the birth of the child) with absolute CYP24A1 methylation | 88 | CYP24A1 | 0.01 | ||||||||
Maternal 25(OH)D concentrations with CYP24A1 methylation with-in pair discordance | 87 | CYP24A1 | 0.001 | |||||||||||||
CYP24A1 promoter methylation variation with variation in neonatal 25(OH)D concentrations | 71 | CYP24A1 | 0.02 | |||||||||||||
Neonatal 25(OH)D concentrations with the mean concentration of CYP24A1 promoter methylation | 147 | CYP24A1 | 1E-06 | |||||||||||||
Neonatal 25-OH‐D discordance with CYP24A1 methylation discordance in monozygotic pairs | 90 | CYP24A1 | 0.02 c | 0.2 | ||||||||||||
85 | CpG_1 d | 0.02 | 0.14 | |||||||||||||
87 | CpG_2.3.4 d | 0.01 | 0.31 | |||||||||||||
81 | CpG_5 d | 0.02 | 0.23 | |||||||||||||
87 | CpG_7.8 d | 0.01 | 0.46 | |||||||||||||
86 | CpG_12.13 d | 0.0002 | 0.9 | |||||||||||||
89 | CpG_17 d | 0.01 | 0.3 | |||||||||||||
72 | CpG_18 d | 0.06 | 0.04 | |||||||||||||
81 | CpG_20.21 d | 0.03 | 0.15 | |||||||||||||
87 | CpG_24 d | 0.002 | 0.69 | |||||||||||||
Chen et al., (24) | 2020 | Randomized clinical trial | USA/ African Americans | Overweight/obese and serum 25(OH)D concentrations of ≤ 50 nmol at the time of screening | Baseline CpG methylation with serum 25(OH)D response | 64 | OSBPL5 | cg07873128 | CHR: 11 | Body | 0.02 f | 0 | < 0.001 | |||
Changes in methylation level with changes in 25(OH)D response | OSBPL5 | cg07873128 | CHR: 11 | Body | 0.6 | |||||||||||
Changes in methylation level with changes in 25(OH)D response | CYP24A1 | cg06368932 | 1stExon, 5’UTR | 0.04 | ||||||||||||
Baseline CpG methylation with serum 25(OH)D response | CYP24A1 | cg22257236 | Body | 0.01 f | 0.003 | |||||||||||
cg18956481 | 5’UTR, 1stExon | 0.01 f | 0.005 | |||||||||||||
cg06368932 | 1stExon, 5’UTR | 0.01 f | 0.01 | |||||||||||||
cg24582168 | Body | 0.008 f | 0.03 | |||||||||||||
cg17997279 | TSS1500 | 0.01 f | 0.04 | |||||||||||||
cg10574372 | Body | -0.006 f | 0.04 | |||||||||||||
CYP27A1 | cg15713912 | Body | -0.02 f | 0.007 | ||||||||||||
cg13648565 | Body | -0.01 f | 0.03 | |||||||||||||
cg13908635 | 3’UTR | -0.008 f | 0.03 | |||||||||||||
cg14553243 | 5’UTR, 1stExon | 0.009 f | 0.04 | |||||||||||||
CYP2R1 | cg25454890 | 1stExon | -0.006 f | 0.03 | ||||||||||||
CYP27B1 | cg07060721 | Body | 0.01 f | 0.02 | ||||||||||||
VDR | cg13173254 | Body, 5’UTR | 0.02 f | 0.005 | ||||||||||||
cg08726078 | Body | 0.01 f | 0.007 | |||||||||||||
cg10037049 | 5’UTR | 0.02 f | 0.01 | |||||||||||||
cg07290465 | Body | 0.007 f | 0.03 | |||||||||||||
cg23190711 | Body, 5’UTR | 0.01 f | 0.03 | |||||||||||||
cg01077720 | ExonBnd, Body | -0.009 f | 0.04 | |||||||||||||
cg06487630 | Body, 5’UTR | -0.01 f | 0.04 | |||||||||||||
cg16998563 | TSS1500 | -0.004 f | 0.048 | |||||||||||||
Suderman et al., (29) | 2016 | Cohort (MoBa) | Norway | Mothers and their newborns | Maternal 25(OH)D concentrations (at 18 weeks gestation) and cord blood DNA methylation | 819 | CYP27B1 | cg01182309 | 7.65E-05 | 0.6 | < 0.001 | |||||
cg18413900 | -0.0001 | 0.6 | 0.04 | |||||||||||||
cg04321714 | 0.0001 | 0.6 | 0.04 | |||||||||||||
cg04905829 | -0.0001 | 0.6 | 0.04 | |||||||||||||
Cohort (ALSPAC) | UK | Mothers and their newborns | Maternal 25(OH)D concentrations (at 28 weeks gestation) and cord blood DNA methylation | 597 | CYP24A1 | cg17997279 | -3.55E-05 | 0.06 | 0.003 | |||||||
CYP27B1 | cg04321714 | -4.49E-05 | 0.06 | 0.003 | ||||||||||||
CYP27A1 | cg02930667 | -4.16E-05 | 0.06 | 0.004 | ||||||||||||
cg03460682 | -2.43E-05 | 0.06 | 0.004 | |||||||||||||
cg22707705 | 0.0004 | 0.2 | 0.02 | |||||||||||||
cg01797727 | -0.0001 | 0.2 | 0.02 | |||||||||||||
Beckett et al., (23) | 2016 | Cross-sectional | Australia | Elderly age (> 65) | Plasma 25(OH)D level (log(x)) with the methylation status of vitamin D-related genes | 80 | CYP2R1 | 102,190 | 11: 14,912,900–14,913,771 g | Promoter | -0.27 i | 0.03 | ||||
CYP2R1 | -0.2 h | 0.03 | ||||||||||||||
CYP2R1 | 0.05 | 0.04 | ||||||||||||||
CYP27B1 | 103,271 | 12: 58,158,855–58,160,000 g | Body | 0.03 i | 0.8 | |||||||||||
CYP27B1 | -0.01 h | 0.9 | ||||||||||||||
CYP27B1 | No statistically significant association | |||||||||||||||
CYP24A1 | 109,362 | 20: 52,789,252–52,790,986 g | Promoter | -0.33 i | 0.04 | |||||||||||
CYP24A1 | 0.02 h | 0.8 | ||||||||||||||
CYP24A1 | 0.06 | 0.02 | ||||||||||||||
VDR | 103,069 | 12: 48,298,645–48,299,537 g | Promoter | 0.25 i | 0.03 | |||||||||||
VDR | 0.26 h | 0.01 | ||||||||||||||
VDR | 0.12 | 0.001 | ||||||||||||||
Wang et al., (25) | 2018 | A mixed case-control and prospective cohort | China | Pulmonary tuberculosis patients as the case group and healthy participants as the control group | Cumulative methylation level at each region with 1,25(OH)2D levels | 240 | CYP24A1 | CYP24A1_1 j | 52,790,591/52,790,815 K | -0.03 | 0.6 | |||||
CYP24A1_2 j | 52,790,767/52,791,019 K | 0.07 | 0.3 | |||||||||||||
CYP27A1 | CYP27A1_1 j | 219,646,982/219,646,721 K | 0.06 | 0.4 | ||||||||||||
CYP27A1_2 j | 219,646,810/219,646,561 K | 0.08 | 0.2 | |||||||||||||
CYP27A1_3 j | 219,646,624/219,646,403 K | 0.13 | 0.045 | |||||||||||||
CYP27A1_4 j | 219,646,465/219,646,204 K | 0.07 | 0.3 | |||||||||||||
CYP27A1_5 j | 219,646,286/219,646,037 K | -0.02 | 0.7 | |||||||||||||
CYP27B1 | CYP27B1_1 j | 58,160,882/58,160,619 K | 0.02 | 0.8 | ||||||||||||
CYP27B1_2 j | 58,160,053/58,159,785 K | 0.12 | 0.06 | |||||||||||||
CYP27B1_3 j | 58,159,890/58,159,688 K | 0.03 | 0.6 | |||||||||||||
CYP2R1 | CYP2R1_1 j | 14,913,830/14,913,634 K | -0.04 | 0.6 | ||||||||||||
CYP2R1_2 j | 14,913,505/14,913,273 K | -0.05 | 0.4 | |||||||||||||
CYP2R1_3 j | 14,913,339/14,913,061 K | -0.05 | 0.5 | |||||||||||||
CYP2R1_4 j | 14,913,116/14,912,845 K | 0.07 | 0.3 | |||||||||||||
VDR | VDR _1 j | 48,299,590/48,299,323 K | 0.01 | 0.9 | ||||||||||||
VDR _2 j | 48,299,412/48,299,179 K | 0.1 | 0.1 | |||||||||||||
VDR _3 j | 48,299,247/48,299,017 K | 0.09 | 0.1 | |||||||||||||
VDR _4 j | 48,299,106/48,298,885 K | 0.02 | 0.7 | |||||||||||||
VDR _6 j | 48,298,733/48,298,464 K | -0.02 | 0.8 | |||||||||||||
Zhou et al., (26) | 2014 | Randomized clinical trial | USA/ non-Hispanic white | white postmenopausal women aged ≥ 55 years | The association between DNA methylation status and adjusted vitamin D response variation | 145 | CYP2R1 | The average methylation level of the 14 examined CpG sites | -0.02 | 0.03 | ||||||
-4 C | -0.13 | 0.03 | ||||||||||||||
+ 28 C | -0.13 | 0.02 | ||||||||||||||
+ 30 C | -0.19 | 0.002 | ||||||||||||||
+ 33 C | -0.12 | 0.046 | ||||||||||||||
+ 40 C | -0.17 | 0.003 | ||||||||||||||
+ 43 C | -0.15 | 0.01 | ||||||||||||||
+ 69 C | -0.13 | 0.03 | ||||||||||||||
+ 80 C | -0.14 | 0.02 | ||||||||||||||
117 | CYP24A1 | −342 C | -0.11 | 0.01 | ||||||||||||
−293 C | -0.13 | 0.03 |