Table 1.
Summary of the main studies on VDR gene methylation in autoimmune and infectious diseases, cancer, and other pathological conditions discussed in the text.
| Disease | Sample Size | Method of Analysis | Genomic Context (VDR Gene) |
Analysis Outcome | Reference | |
|---|---|---|---|---|---|---|
| Autoimmune diseases | Rheumatoid arthritis | 122 RA vs. 123 CTRs |
MethylTarget | CpG sites in the promoter region |
VDR methylation levels in RA patients were significantly reduced compared to CTRs |
[26] |
| 35 RA vs. 41 CTRs |
Pyrosequencing | 10 CpG sites in the promoter region | Methylation analysis revealed no significant differences between RA patients compared to CTRs | [22] | ||
| Multiple sclerosis | 23 RRMS vs. 12 CTRs |
Bisulfite cloning sequencing |
23 CpG sites in main promoter, 10 CpG sites in alternative promoter located at non-coding exon 1c | Methylation levels in VDR alternative promoter were significantly higher in RRMS patients compared to CTRs | [23] | |
| Behcet’s disease | 48 BD vs. 60 CTRs |
MeDIP-qPCR | All CpG sites in the promoter region from −800 bp to +200 bp relative to the TSS | Methylation analysis revealed no significant differences between BD patients compared to CTRs | [30] | |
| Infectious diseases | Tuberculosis disease | 27 TB vs. 30 CTRs |
Bisulfite cloning sequencing |
16 CpG sites in VDR | TB patients were in the hypermethylation state compared to CTRs | [31] |
| 43 TB vs. 33 CTRs |
MS-PCR | The location of CpG sites and CGIs present in the VDR sequence were identified by DBCAT | Methylation analysis revealed a hypermethylation in TB patients and hypomethylation in CTRs | [13] | ||
| 122 TB vs. 118 CTRs |
Illumina MiSeq | 60 CpG sites in the promoter region (48,299,590–48,298,885) |
Methylation levels were significantly lower in TB patients compared to CTRs | [32] | ||
| Hand, foot, and mouth disease | 116 HFMD vs. 60 CTRs | MethylTarget | 12 CpGs in promoter region from −638 bp to −545 bp relative to the TSS | Methylation levels of VDR promoter in HFMD were lower compared to CTRs | [33] | |
| HIV | TCs obtained from healthy volunteers | Pyrosequencing | CpG in VDR promoter region from −512 bp to −28 bp relative to the TSS | HIV-infected TCs showed increased methylation in CpG sites | [34] | |
| Cancer | Breast cancer | 15 BCT vs. 7 NBT |
MS-PCR | 3 CGIs in VDR promoter region from −789 bp to +380 bp relative to the TSS | Methylation levels of VDR promoter in BCT were significantly higher compared to NBT | [35] |
| Adrenocortical carcinoma |
23 AT vs. 3 NAT |
BSP | 42 CpG sites in VDR promoter region from −693 bp to −65 bp relative to the TSS | 27/42 CpG sites were methylated in 3 ACCs | [36] | |
| Hepatocellular carcinoma |
15 HC vs. 15 CLD vs. 15 NT | MS-PCR | VDR promoter | Methylation levels of VDR promoter in HCC were significantly higher compared to other studies groups | [37] | |
| Parathyroid adenomas |
15 PAT vs. 4 NPT |
BSP | 31 CpG sites in VDR promoter region from −538 bp to −79 bp relative to the TSS | There was no significant methylation in the promoter region of VDR in parathyroid adenomatous tissues | [38] | |
| Colorectal cancer | 75 CCT vs. 75 NE |
MS-PCR | VDR promoter | Hypermethylation of VDR was detected in 28 (37,33%) of 75 cases | [39] | |
| Others | Osteoporosis | 25 OP vs. 25 CTRs |
Pyrosequencing | 6 CpG sites in VDR promoter | No statistically significant difference was found in the methylation pattern between OP and CTRs | [40] |
| Male infertility | 69 ID vs. 37 CTRs |
MS-PCR | 3 CGIs in VDR promoter | VDR methylation percentage was increased with the severity of the diagnosis, correlating with lower sperm motility and concentration, and altered sperm morphology | [41] | |
| 60 IID vs. 60 CTRs |
MS-PCR | 1 CGI in VDR promoter | Methylation levels of VDR promoter in IID were significantly higher compared to CTRs | [42] | ||
| Recurrent kidney stone formation |
30 consecutive recurrent kidney stone formers vs. 30 CTRs | MS-HRM | 16 CpG sites in VDR promoter | Two VDR promoter regions were hypermethylated in patients with consecutive recurrent kidney stone formers compared to CTRs | [43] | |
| Type 2 diabetes mellitus |
272 T2DM vs. 272 CTRs | MS-HRM | 27 CpG sites in VDR promoter | Increased methylation levels of VDR were associated with decreased levels of serum insulin |
[44] |
Abbreviations: RA, rheumatoid arthritis; CTRs, control groups; VDR, vitamin D receptor; RRMS, relapsing-remitting multiple sclerosis; BD, Behcet’s disease; MeDIP-qPCR, methylated DNA immunoprecipitation-real time PCR; TSS, transcription start site; TB, tuberculosis; MS-PCR, methylation specific-polymerase chain reaction; CGIs, CpG islands; DBCAT, DataBase of CGIs and analytical tool; HFMD, hand, foot, and mouth disease; HIV, human immunodeficiency virus; TCs, Tcell; BCT, breast cancer tissue; NBT, normal breast tissue; AT, adrenal tumors; NAT, normal adrenal tissue; BSP, bisulfite sequencing PCR; ACC, adrenocortical carcinoma; HC, hepatocellular carcinoma; CLD, chronic liver disease; NT, normal tissue; PAT, parathyroid adenomas tissue; NPT, normal parathyroid tissue; CCT, colorectal cancer tissue; NE, normal epithelium; OP, osteoporosis; ID, infertility disease; IID, idiopathic infertility disease; MS-HRM, methylation-sensitive high-resolution melting; T2DM, type 2 diabetes mellitus.