Table 2.
Expression profiling of candidate genes in the lung and periphery. (+) indicates the gene is expressed in the cell type used and (−) indicates the gene expression at mRNA level is not detected following 40 cycles of PCR. PCR profiling of gene transcripts in the human lung demonstrates expression of all candidates except CCDC38, for which two sets of primers were designed and tested under different optimization conditions. None of these assays detected expression of CCDC38 in the cell types analysed. The SNRPF gene neighbouring CCDC38 and harbouring SNPs with strong LD with CCDC38’s sentinel SNP was assayed instead. All PCR products were sequence verified. Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) was used as a positive control for the cDNA and was expressed in all tissues. HASM: Human airway smooth muscle. HBEC: Human bronchial epithelial cells. PBMC: peripheral blood mononuclear cells.
| Sentinel SNP (relationship to gene) |
Chr. | Gene | Putative Function of encoded protein |
Tissue | |||
|---|---|---|---|---|---|---|---|
| Lung | HASM | HBEC | PBMC | ||||
| rs993925 (intron) |
1 | TGFB2 | Cytokine with roles in pro-fibrotic cytokine modulating epithelial repair mechanisms and extracellular matrix homeostasis including collagen deposition40 |
+ | + | − | − |
| rs2284746 (intron) |
1 | MFAP2 | Major antigen of elastin-associated microfibrils17 and a candidate for involvement in the etiology of inherited connective tissue diseases. |
+ | + | + | − |
| rs12477314 (downstream) |
2 | HDAC4 | Deacetylase of histone surrounding DNA thus influencing transcription factor access to the DNA possibly repressing gene transcription. |
+ | + | + | + |
| rs1344555 (intron) |
3 | EVI1 | Zinc finger transcription factor, encoded as part of MDS1/EVI1 complex locus (MECOM). |
+ | + | + | − |
| rs1529672 (intron) |
3 | RARB | Nuclear retinoic acid receptor responsive to retinoic acid, a vitamin A derivative and which also controls cell proliferation and differentiation. |
+ | + | + | + |
| rs153916 (intron) |
5 | SPATA9 | Initially identified as a mediator of spermatogenesis, other family members may have a role in pancreatic development and β-cell proliferation41 |
+ | + | + | + |
| rs2798641 (intron) |
6 | ARMC2 | Function unknown although other family members have been identified as having roles in cell signalling, protein degradation and cytoskeleton functions42 |
+ | + | + | + |
| rs2857595 (upstream) |
6 | NCR3 | Required for efficient cytotoxicity responses by natural killer cells against normal cells and tumours43 |
+ | − | − | + |
| rs6903823 (intron) |
6 | ZKSCAN3 | Transcription factor involved in cell growth/cell cycle/signal transduction |
+ | + | + | + |
| rs7068966 (intron) |
10 | CDC123 | Homologue in yeast shown to be a critical control protein modulating Eukaryotic initiation factor 2 in times of cell stress |
+ | + | + | + |
| rs11001819 (intron) |
10 | C10orf11 | Function unknown | + | + | + | + |
| rs11172113 (intron) |
12 | LRP1 | Potentially diverse roles including cell signalling and migration44 |
+ | + | + | + |
| rs1036429 (intron) |
12 | CCDC38 | Function unknown although other family members involved in a diverse array of functions skeletal and motor function45 |
− | − | − | − |
| rs1036429 (r2=0.96 with rs4762633 in SNRPF) |
12 | SNRPF | Small nuclear ribonucleoprotein F | + | + | + | + |
| rs12447804 (intron) |
16 | MMP15 | Member of a large protease family with diverse functional roles via protease activity and specificity including; tissue remodelling, wound healing, angiogenesis, and tumor invasion. |
+ | + | + | − |
| rs2865531 (intron) |
16 | CFDP1 | Craniofacial Development Protein 1 | + | + | + | + |
| rs9978142 (upstream) |
21 | KCNE2 | KCNQ1-KCNE2 K+ channels may modulate transepithelial anion secretion in Calu3 airway epithelial cells46. |
+ | − | − | + |
|
Reference gene |
12 | GAPDH | + | + | + | + | |