Table 4. Interactions of two different CDK4 SNPs (rs2270777 and rs2069502) carried by a single allele with genes, for which differential baseline gene expression is associated with low 1-month change in IGF-I SDS (⩽Q1 versus Q2–Q4).
|
Signaling pathways |
GHD: canonical pathways |
TS: canonical pathways |
|---|---|---|
| Carriage of rs2270777 1769 probe sets (P<0.05) Allele A | Carriage of rs2069502 473 probe sets (P<0.05) Allele A | |
| p53 | — | — |
| Wnt | — | q=1.3 × 10–5 |
| GR | — | — |
| IGF-I (MAPK) | q=1.0 × 10–5 | — |
|
Carriage of rs2270777 1112 probe sets (P<0.05)
Allele G |
Carriage of rs2069502 1194 probe sets (P<0.05)
Allele G |
|
| p53 | — | q=6.8 × 10–6 |
| Wnt | — | — |
| GR | q=1.2 × 10–5 | — |
| IGF-I (MAPK) | — | — |
Abbreviations: GHD, growth hormone deficiency; GR, glucocorticoid receptor; IGF-I, insulin-like growth factor-I; MAPK, mitogen-activated protien kinase; Q, quartile; SDS, s.d. score; SNP, single-nucleotide polymorphism; TS, Turner syndrome.
Number of gene expression probe sets associated with carriage of SNP alleles in baseline gene expression (analysis of variance, P<0.05). False discovery-modified P-values (q) based on hypergeometric tests are shown. In low IGF-I responders to growth hormone treatment, changes in several genes differ within four signaling pathways, IGF-I (via MAPK/GRB2/SOS, which are major pathways mediating IGF-I signaling), p53, Wnt and GR, depending on the carriage of the specified CDK4 SNP allele.