Table 2.
Immunologically relevant genes and transcription factors that were identified as modifiers of the CFTR-mediated basic defect among F508del-CFTR homozygous CF patients.
| Functional category | Gene | Association observed with | Reference |
|---|---|---|---|
| Ligands | CD14 | CFTR activity/intestinal tissue [C] Non-CFTR mediated residual chloride secretion/intestinal tissue [D] |
[13] |
| TNFA | CFTR activity/nasal epithelium [B] | [13] | |
| IL1B | CFTR activity/intestinal tissue [C] | [13, 39] | |
| TGFB1 | Non-CFTR mediated residual chloride secretion/intestinal tissue [D] | [13] | |
| IL8 | CFTR activity/nasal epithelium [B] | [13] | |
|
| |||
| Membrane-bound receptors | TLR4 | ENaC activity/nasal epithelium [A] CFTR activity/nasal epithelium [B] CFTR activity/intestinal tissue [C] |
[13] |
| TNFR1 | ENaC activity/nasal epithelium [A] CFTR activity/nasal epithelium [B] CFTR activity/intestinal tissue [C] Non-CFTR mediated residual chloride secretion/intestinal tissue [D] |
[13] | |
| CD95 | ENaC activity/nasal epithelium [A] CFTR activity/nasal epithelium [B] CFTR activity/intestinal tissue [C] Non-CFTR mediated residual chloride secretion/intestinal tissue [D] |
[13] | |
| IFNGR1 | CFTR activity/nasal epithelium [B] CFTR activity/intestinal tissue [C] |
[13, 39] | |
| TLR5 | CFTR activity/nasal epithelium [B] Non-CFTR mediated residual chloride secretion/intestinal tissue [D] |
[13] | |
| TLR9 | CFTR activity/intestinal tissue [C] Non-CFTR mediated residual chloride secretion/intestinal tissue [D] |
[13] | |
|
| |||
| Transcription factors | STAT3 | CFTR activity/intestinal tissue [C] | [13, 39] |
| EHF | ENaC activity/nasal epithelium [A] CFTR activity/intestinal tissue [C] |
[45] | |
[A]: the association was observed in a case-reference study comparing F508del-CFTR homozygotes with high versus low change of the potential upon superfusion of the nasal epithelium with amiloride as assessed by nasal potential difference measurement. Please see [13] for details.
[B]: the association was observed in a case-reference study comparing F508del-CFTR homozygotes with presence versus absence of a change of the potential upon superfusion of the nasal epithelium with chloride-free solution and isoproterenol as assessed by nasal potential difference measurement. Please see [13] for details.
[C]: the association was observed in a case-reference study comparing F508del-CFTR homozygotes with presence versus absence of DIDS-insensitive residual chloride secretion as assessed by intestinal current measurement of rectal suction biopsies. Please see [13] for details.
[D]: the association was observed in a case-reference study comparing F508del-CFTR homozygotes with presence versus absence of DIDS-sensitive residual chloride secretion of the intestinal tissue as assessed by intestinal current measurement of rectal suction biopsies. Please see [13] for details.