Table 2.
Genetic associations of COPD
| Gene* | Descriptors† | Function | COPD phenotype | References | |
|---|---|---|---|---|---|
| CHRNA3/5 | rs8034191 rs1051730 |
Airflow obstruction with low FEV1; FEV1 decline | [33] | ||
| EPHX1 | rs1051740 rs2234922 |
Tyr213His His139Arg |
Enzyme activity ↓ Enzyme activity ↑ |
Emphysema; UZDE; FEV1 decline | [9,41,86-90] |
| GC | rs4588 rs7041 |
Thr436Lys Asp432Glu |
Conversion to MAF ↓ | Emphysema; airflow obstruction with low FEV1; FEV1 decline | [91-93] |
| GSTM1 | Gene deletion | Null | No protein | Emphysema; chronic bronchitis | [94-96] |
| GSTP1 | rs947894 | Ile105Val | Enzyme activity ↑ | UZDE; airflow obstruction with low FEV1; FEV1 decline | [9,40,95,97-99] |
| HHIP | rs1828591 rs13118928 |
Airflow obstruction with low FEV1; FEV1 decline | [33,39] | ||
| HMOX1 | Microsatellite in promoter | GT(n) | Gene transcription ↑ Enzyme activity ↓ |
Emphysema; airflow obstruction with low FEV1; FEV1 decline | [100,101] |
| IL1RN | VNTR tandem repeat | COPD | [40] | ||
| MMP1 | rs1799750 | G-1607GG | Gene transcription ↑ | UZDE; FEV1 decline | [9] |
| MMP9 | rs3918242 | C-1562T | Gene transcription ↑ | UZDE; airflow obstruction with low FEV1 | [10,102,103] |
| SERPINA3 | rs4934 rs17473 rs1800463 |
Ala-15Thr Pro227Ala Leu55Pro |
Altered protein Protein level ↓ Protein level ↓ |
Altered airway resistance | [104,105] |
| SERPINE2 | Various | N/A | N/A | Airflow obstruction with low FEV1 | [37,47] |
| SOD3 | rs1799895 | Arg213Gly | Protein level ↑ | Airflow obstruction with low FEV1 | [23] |
| SFTPB | rs1130866 rs2118177 |
Thr131Ile | Altered protein | Airflow obstruction with low FEV1; dyspnoea in emphysema; exacerbation frequency | [86,87,106] |
| TGFB | rs1800469 rs1982073 |
C-509T C613T |
Protein level ↑ Protein level ↑ |
Airflow obstruction with low FEV1; dyspnoea in emphysema | [40,87,107] |
| TNFA | rs1800629 | G-308A | Protein level ↑ | Emphysema; chronic bronchitis; airflow obstruction with low FEV1 | [40,42,108-110] |
*Genes with evidence of an effect at genome-wide, meta-analysis or post-Bonferroni-correction level are in bold. †Most modern studies report these associations using the reference SNP number (rs...), but older studies often refer to the nucleotide change, whose nomenclature lists the more common allele, followed by the position of the SNP within the gene, and then the least common allele. For example, for TNFA, G-308A refers to a polymorphism at position -308 in the gene, which changes a G (guanine) residue to an A (adenine). The negative position indicates that it is in the promoter region. Alternatively, a SNP might be described by the effect it has on its protein product. This follows a similar system to that of nucleotide changes, such that, for example, in SOD3 Arg213Gly indicates a change from an arginine to a glycine residue at position 213 within the protein. Where such descriptors are common in the literature, both the rs number and these are shown. Abbreviations: GC, vitamin D binding protein; HMOX1, heme oxygenase; SFTPB, surfactant protein B; SOD, superoxide dismutase; TGFB, transforming growth factor β; UZDE, upper zone dominant emphysema.