Table 2.
Ten significant differentially methylated CpG dinucleotides and average methylation of introns 2 and 7, in Cushing’s syndrome (CS) patients compared to controls
| Cushing patients Cured (n = 23) |
Active (n = 9) |
Controls (n = 32) |
P | P1 | P2 | |
|---|---|---|---|---|---|---|
| Intron2reg1CpG-3 | 94.7 % (45.8–95.5) | 94.8 % (94.5–95.4) | 95.5 % (72.2–97.1) | 0.014 | 0.001 | ns |
| Intron2reg1CpG-4 | 91.2 % (35.4–93.8) | 92.2 % (89.6–93.6) | 94.1 % (65.4–96.0) | 0.006 | <0.001 | ns |
| lntron2reg1CpG-5 | 93.7 % (82.5–96.1) | 95.1 % (87.7–97.2) | 95.5 % (89.7–100) | ns | 0.002 | ns |
| Intron2reg2CpG-3 | 70.4 % (62.7–78.3) | 64.8 % (55.2–71.6) | 72.2 % (61.8–77.0) | 0.001 | ns | 0.002 |
| Intron2reg3CpG-4 | 82.1 % (79.0–100) | 82.2 % (80.8–82.8) | 83.1 % (81.0–100) | 0.012 | 0.001 | ns |
| Intron5 CpG-1 | 4.8 % (3.03–7.5) | 4 % (2.8–4.7) | 5.2 % (3.8–7.9) | 0.000 | ns | 0.001 |
| Inlron7 CpG-1 | 91.88 % (73.0–100) | 90.6 % (76.3–98.2) | 98.5 % (86.3–100) | <0.001 | 0.001 | ns |
| Intron7 CpG-2 | 74.4 % (53.1–83.7) | 72.8 % (51.5–77.3) | 79.0 % (54.4–87.1) | 0.001 | 0.002 | ns |
| Intron7 CpG-6 | 63.4 % (43.0–73.4) | 53.5 % (43.8–63.3) | 66.7 % (51.6–73.2) | <0.001 | ns | 0.007 |
| Intron7 CpG-7 | 62.3 % (44.3–87.1) | 56.3 % (48.8–60.0) | 62.2 % (48.7–74.0) | 0.002 | ns | 0.006 |
| Average methylation of intron 2 | 92.37 %, | 91.80 % | 93.34 % | 0.03 | 0.03 | ns |
| Average methylation of intron 7 | 77.08 % | 73.74 % | 79.71 % | <0.01 | 0.02 | ns |
Values indicate the percent of FKBP5 DNA methylation at the indicated CpG dinucleotides and are expressed as median (range). A CpG site (shorth and for C-phosphate-G) refers to a cytosine nucleotide followed by a guanine nucleotide in the linear sequence of bases along the length of DNA. Cytosines in CpG dinucleotides can be methylated to alter gene function in animals and plants, where lower CpG methylation generally correlates with higher gene expression
Intron 2 is divided into four regions that reflect four independent bisulfite pyrosequencing assays
Five significant differentially methylated CpG dinucleotides were located in intron 2, one in intron 5 and four in intron 7
Reg = region
ns= not significant
p = significance between active CS patients and controls
p1 = significance between cured CS patients and controls
p2 = significance between cured CS patients and active CS patients