Table 1.
Candidate gene association studies and susceptibility to tuberculosis
| Gene |
Variants |
Validate* |
Function of varianty |
Comments |
|
|---|---|---|---|---|---|
| TB |
Other diseases |
||||
| Binding, receptors, and signaling | |||||
| MBL | Alleles B, C, and D and promoter | Variable | Variable | Y | Heterogeneous results from various studies |
| Surfactant protein | Multiple in Sp-A and Sp-D | N | N | N | |
| DC-SIGN | −871G, −336A | N | Y, dengue | P, expression | |
| P2XA7 | −762 | N | N | N | |
| A1513C (E469A) | Y | N | Y | Alters ATP-induced macrophage functions, including MTb killing | |
| TLR2 | G2258A (R753Q) | N | Y, lyme | Y, signaling | |
| Intron 2 GT microsatellite | N | N | P, expression | ||
| C597T (N199N) | N | Y, leprosy | N | ||
| TIRAP/MAL | C539T (S180L) | Y | Y, malaria, bacteremia, pneumococcal empyema or baceremia | Y, signaling | |
| C558T (A186A) | N | N | P, signaling | Associated with TB meningitis | |
| Cytokines/chemokine | |||||
| IFN-γ | þ874A, −1616T, þ3234T | 874, likely. Others: N | N | Y, 874 and IFN-γ expression | 874 variant affects function and has the most promising association with Tb, but not replicated in all studies |
| IFN-γR1 | Microsatellite | N | N | N | |
| T-56C | Y | N | N | ||
| IL-1β/IL-1RA | Multiple | N | Y, H pylori, HBV | P, for some alleles | |
| IL-12-Rβ1 | Q214R, G378R, and M365T | Variable | N | P, signaling | |
| IL-12B | Multiple | N | N | P | |
| IL-10 | A-1082G, A-592C | Variable | Y, leprosy | P, expression | |
| CCL2 (MCP1) | A-2518G | Y | N | Y, expression | Variant may inhibit IL-12 production |
| TNF-α | G-308A, G-238A | Variable | Y, malaria, leprosy | P | |
| TNFR1 | Multiple | Y | N | P, signaling | |
| IL-8 | T-251A | N | Y, RSV | N | |
| Other | |||||
| HLA | Multiple studies demonstrate an association. Reviewed elsewhere | ||||
| VDR | Fok1, BsmI, ApaI, TaqI | Variable | Y, bone mineral density | P | Heterogeneous results from various studies |
| Slc11a1 (NRAMP1) | 3′UTR, D543N, INT4, and 5′(GT)n | Y | Y, Neisseria, leishmania | P, transcription | Best documented association with 15 studies. Functional data are not clear |
| Ube3a | Multiple | Y | N | N | |
| SP110 | Two variants | Y | N | N | Identified from mouse sst1 locus |
See text for references and more detail.
N, no; Y, yes; P, possible effect.
*
Validation refers to whether the genetic findings were replicated in another MTb cohort or with a separate study design (family-based or case–control).
Validation is also noted if it occurred with another disease (other diseases).
†
Function refers to whether the variant is associated with altered function of the gene, either through regulation of expression levels or through a non-synonymous coding region polymorphism that alters the function of the gene.