Table 1
Basic characteristics and gene mutations for pulmonary artery hypertension patients.
| Number | Sex | Age | BMPR2 | ALK-1 | KCNK3 | CAV1 | ENG |
|---|---|---|---|---|---|---|---|
| 1 | M | 54 | (－) | (－) | (－) | (－) | (－) |
| 2 | F | 67 | (－) | (－) | (－) | (－) | (－) |
| 3 | F | 55 | (－) | (－) | (－) | ex3 A216P | (－) |
| 4 | F | 37 | (－) | (－) | (－) | (－) | (－) |
| 5 | F | 48 | (－) | (－) | (－) | (－) | (－) |
| 6 | F | 49 | (－) | (－) | (－) | (－) | (－) |
| 7 | F | 39 | (－) | (－) | (－) | (－) | (－) |
| 8 | F | 36 | (－) | (－) | (－) | (－) | (－) |
| 9 | F | 45 | (－) | (－) | (－) | (－) | (－) |
| 10 | F | 71 | (－) | (－) | (－) | (－) | (－) |
| 11 | F | 43 | (－) | (－) | c.-2C>A (IVS1-2 C>A) | (－) | (－) |
| 12 | M | 48 | (－) | (－) | (－) | (－) | ex8 D366H |
| 13 | M | 25 | G410DfsX1 | (－) | (－) | (－) | (－) |
| 14 | F | 57 | (－) | (－) | (－) | (－) | (－) |
| 15 | F | 48 | (－) | ex7 L300P | (－) | (－) | ex8 D366H |
| 16 | F | 62 | (－) | ex4 S110PfsX40 | (－) | (－) | (－) |
| 17 | F | 56 | (－) | (－) | (－) | (－) | (－) |
| 18 | F | 42 | (－) | ex7 E295Afs96X | (－) | (－) | (－) |
| 19 | F | 51 | (－) | (－) | (－) | (－) | (－) |
| 20 | F | 39 | (－) | (－) | (－) | (－) | ex8 D366H |
Table 2
Comparison of variables between five gene subgroups.
| Variables | All | BMPR2 | ALK1 | KCNK3 | CAV1 | ENG | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (+) | (–) | P value | (+) | (–) | P value | (+) | (–) | P value | (+) | (–) | P value | (+) | (–) | P value | ||
| Count | 20 | 1 (5%) | 19 (95%) | 3 | 17 | 1 | 19 | 1 | 19 | 3 | 17 | |||||
| Male | 3 (15%) | 1 (100%) | 2 (10.5%) | 0.1500 | – | 3 (17.7%) | 1.0000 | – | 3 (15.8%) | 1.0000 | – | 3 (15.8%) | 1.0000 | 1 (33.3%) | 2 (11.8%) | 0.4035 |
| Female | 17 (85%) | – | 17 (89.5%) | – | 3 (100%) | 14 (82.4%) | 1 (100%) | 16 (84.2%) | – | 1 (100%) | 16 (84.2%) | – | 2 (66.7%) | 15 (88.2%) | ||
| Age | 48.6 ± 11.1 | 25 | 49.8 ± 9.9 | – | 50.7 ± 10.3 | 48.2 ± 11.5 | 0.7368 | 43.0 | 48.9 ± 11.3 | – | 55.0 | 48.3 ± 11.3 | – | 45.0 ± 5.2 | 49.2 ± 11.9 | 0.5570 |
| Height | 159.2 ± 6.4 | 161 | 159.1 ± 6.6 | – | 156.0 ± 3.6 | 159.7 ± 6.7 | 0.3683 | 154.1 | 159.9 ± 6.5 | – | 155.0 | 159.4 ± 6.5 | – | 163.3 ± 7.1 | 158.4 ± 6.2 | 0.2292 |
| Weight | 58.8 ± 9.3 | 62 | 58.6 ± 9.5 | – | 49.7 ± 1.2 | 60.4 ± 9.2 | 0.0633 | 55.6 | 59.0 ± 9.5 | – | 64.0 | 58.5 ± 9.5 | – | 62.8 ± 14.8 | 58.1 ± 8.5 | 0.4315 |
[i] Values are expressed as mean (μ) ± standard deviation for continuous variables and numbers (%) for categorical variables.
Figure 1
The DAVID database was used for functional annotation. Panel A. Mutated genes in this study, including BMPR2, ALK1, KCNK3, CAV1, and ENG were entered into the gene list. Common associated diseases included pulmonary hypertension, liver cirrhosis, as well as associated hepatopulmonary syndrome. Panel B. Mutated genes in our study and their associated protein interactions.
Activin A receptor type 1 (ACVR1); bone morphogenetic protein 7 (BMP7); transforming growth factor beta receptor 1 (TGF-β1).
Figure 2
Gene cluster and ontology outputs of the five locus variants, as analysed by the DAVID database. Panel A. All mutated genes in this study belonged to the ‘disease mutation’ gene cluster (-log P value: 2.72). Panel B. PAH gene ontology of mutated genes in this study. Gene ontology reports ‘negative regulation of nitric-oxide synthase activity’ (–log P value: 2.85), ‘negative regulation of endothelial cell proliferation’ (–log P value: 2.28), ‘positive regulation of BMP signalling pathway’ (–log P value: 2.26), ‘positive regulation of pathway-restricted Smad protein phosphorylation’ (–log P value: 2.07), ‘vasculogenesis’ (–log P value: 2.00), ‘negative regulation of TGF-β receptor signalling pathway’ (–log P value: 1.96), ‘regulation of cell proliferation’ (–log P value: 1.48), and ‘BMP binding’ (–log P value: 2.74).
Bone morphogenetic protein (BMP); transforming growth factor beta receptor 1 (TGF-β1).
Figure 3
GEO profile database associated with gene mutations and expressions. Panel A. GEO profile database reports that BMPR2 mutation is associated with PAH expression. Panel B. BMP2 (39998_at) expression is associated with idiopathic pulmonary artery hypertension (IPAH). Panel C. CVA1 (212097_at) expression could lead to IPAH.
Abbreviations: Bone morphogenetic protein receptor (BMPR).
Table 3
Mutation positions for PAH patients receiving pedigree survey.
| Sample ID | Fragment | Gene Position | RefSeq Base Call | Base Call | Amino Acid Change | DNA concentration (ng/μl) |
|---|---|---|---|---|---|---|
| P11 | KCNK3ex1 | IVS1-2 | C | A | IVS1-2 C>A | 136 |
| P12 | ENGex8 | 1096 | G | C | D366 (D, H) | 113 |
| P13 | BMPR2ex9 | 1229 | G | del G | G410DfsX1 | 106 |
Figure 4
Location of gene mutation and family pedigree of volunteer PAH patients. Arrows indicate PAH patients in our study. Panel A. Gene mutation location of P11 is at IVS1–2 C>A in the KCNK3ex1 fragment. Panel B. P12 has a gene mutation located at D366(D, H) in the ENGex8 fragment. Panel C. P13 has s gene mutation located at G410DfsX1 in the BMPR2ex13 fragment.