Table 1 Characteristics of the included studies according to the gene methylation sites and its effect on vitamin D levels

Wjst et al., (27)

Cross-sectional

Germany

25(OH)D3 level with methylation rate of CpG sites

CYP27B1

CpG 15–17 ^b

0.11

All p-values < 0.05

O’Brien et al., (28)

Case-cohort sample

USA/ Non-Hispanic white

All cases were women

25(OH)D level and with methylation level of CpGs

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)

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

RXRA

CpG 4/5 ^b

9: 136355593,600 +

-3.29

0.03

Novakovic et al., (30)

Cohort

Australia

Mothers and their newborns

Maternal 25(OH)D concentrations (at the birth of the child) with absolute CYP24A1 methylation

CYP24A1

0.01

Maternal 25(OH)D concentrations with CYP24A1 methylation with-in pair discordance

CYP24A1

0.001

CYP24A1 promoter methylation variation with variation in neonatal 25(OH)D concentrations

CYP24A1

0.02

Neonatal 25(OH)D concentrations with the mean concentration of CYP24A1 promoter methylation

CYP24A1

1E-06

Neonatal 25-OH‐D discordance with CYP24A1 methylation discordance in monozygotic pairs

CYP24A1

0.02 ^c

0.2

CpG_1 ^d

0.02

0.14

CpG_2.3.4 ^d

0.01

0.31

CpG_5 ^d

0.02

0.23

CpG_7.8 ^d

0.01

0.46

CpG_12.13 ^d

0.0002

0.9

CpG_17 ^d

0.01

0.3

CpG_18 ^d

0.06

0.04

CpG_20.21 ^d

0.03

0.15

CpG_24 ^d

0.002

0.69

Chen et al., (24)

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

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)

Cohort (MoBa)

Norway

Mothers and their newborns

Maternal 25(OH)D concentrations (at 18 weeks gestation) and cord blood DNA methylation

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

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)

Cross-sectional

Australia

Elderly age (> 65)

Plasma 25(OH)D level (log(x)) with the methylation status of vitamin D-related genes

CYP2R1

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

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

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

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)

 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

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)

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

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

CYP24A1

−342 C

-0.11

0.01

−293 C

-0.13

0.03