Table 1.
Leprosy-associated genes with functional evidence or replicated status.
| Gene | Name | Identification strategy | Population sample (Reference) | Gene function/pathway |
|---|---|---|---|---|
| CARD9 | Caspase recruitment domain family member 9 | GWAS—protein-coding variants | Chinese case-control (21) | Regulatory function in cell apoptosis and induction of NF-kB |
| FLG | Filaggrin | GWAS—protein-coding variants | Chinese case-control (21) | The structural component of the epidermis |
| HIF1A | Hypoxia-inducible factor 1 alpha subunit | GWAS—protein-coding variants | Chinese case-control (22) | Regulator of cellular and systemic homeostatic response to hypoxia; inflammation, autophagy, and immune reactions |
| HLA-C | Major histocompatibility complex (MHC), class-I. Human leukocyte antigen (HLA) | Association scan of the HLA locus | Vietnamese family-based (23) Indian case-control (23) |
Immune recognition and antigen presentation |
| HLA-DR-DQ | MHC, class-II. HLA | GWAS | Chinese case-control (20) | Immune recognition and antigen presentation |
| Association scan | Indian case-control (24) | |||
| Candidate gene analysis | Vietnamese family-based (25) | |||
| IL10 | Interleukin 10 | Candidate gene analysis | Brazilian case-control (26) | Immunoregulation; downregulates Th1 response and induces B-cell survival, proliferation, and antibody production |
| Brazilian case-control (27) | ||||
| Indian case-control (28) | ||||
| Brazilian family-based; meta-analysis (29) | ||||
| IL12B | Interleukin 12B | GWAS | Chinese case-control (30) | Activator of NK and T-cells. Inducer of Th1 immune response |
| IL18RAP/IL18R1 | Interleukin 18 receptor accessory protein/interleukin 18 receptor 1 | GWAS | Chinese case-control (30) | The receptor of IL18, a proinflammatory cytokine that induces cell-mediated immune response |
| IL23R | Interleukin 23 receptor | GWAS—protein-coding variants | Chinese case-control (21) | Binds to IL23 activating NK and T-cells; pro-inflammatory receptor |
| GWAS | Chinese case-control (31) | |||
| IL27 | Interleukin 27 | GWAS—protein-coding variants | Chinese case-control (21) | Modulator of T-cell differentiation |
| KIR (2DS1, 2DS2, 2DS3) | Killer immunoglobulin-like receptor (KIR) | Candidate gene analysis | Brazilian case-control (32) | Regulatory molecules of NK cells surface; mediates NK reactivity against target cells; depending on HLA-I ligands |
| Brazilian case-control (33) | ||||
| LACC1—CCDC122 | Laccase domain containing—coiled-coil domain containing 122 | GWAS | Chinese case-control (20) | LACC1 is involved in fatty-acid oxidation with inflammasome activation, ROS production, and modulation of bactericidal activity of macrophages. CCDC122 function is presently unknown |
| Chinese case-control (34) | ||||
| Candidate gene analysis | Brazilian family-based (35) | |||
| Brazilian case-control (35) | ||||
| Vietnamese family-based (25) | ||||
| GWAS—protein-coding variants | Chinese case-control (22) | |||
| LRRK2 | Leucine rich repeat kinase 2/Dardarin | GWAS | Chinese case-control (20) | Regulation of autophagy, inflammasome activity, and production of ROS and inflammatory cytokines |
| Candidate gene analysis | Indian case-control (36) | |||
| Chinese case-control (37) | ||||
| Vietnamese family-based (38) | ||||
| LTA | Lymphotoxin-α | Genome-wide linkage analysis | 2 Vietnamese family-based (39) | Pro-inflammatory cytokine, it mediates inflammatory response |
| Brazilian case-control (39) | ||||
| Indian case-control (39) | ||||
| MRC1 | Mannose receptor C-type 1 | Candidate gene analysis | Vietnamese family-based (40) | Membrane receptor that mediates carbohydrate recognition |
| Brazilian case-control (40) | ||||
| NCKIPSD | NCK interacting protein with SH3 domain | GWAS—protein-coding variants | Chinese case-control (21) | Signal transduction; regulation of cytoskeleton |
| NOD2 | Nucleotide-binding oligomerization domain containing 2 | GWAS | Chinese case-control (20) | Recognition of LPS bacterial structure and activation of NF-kB |
| Candidate gene analysis | Brazilian family-based (35) | |||
| Brazilian case-control (35) | ||||
| Vietnamese family-based (25) | ||||
| PARK2 | Parkin RBR E3 ubiquitin protein ligase | Genome-wide linkage analysis | Vietnamese family-based (41) | E3 ubiquitin-protein ligase with a role on proteasome function, mitophagy, intracellular bacterial clearance, and mitochondrial antigen presentation |
| Brazilian case-control (41) | ||||
| Candidate gene analysis | 2 Indian case-control (42) | |||
| Vietnamese family-based (43) | ||||
| RAB32 | RAB32, member RAS oncogene family | GWAS—protein-coding variants | Chinese case-control (21) | Protein metabolism, vesicle-mediated transport and autophagy |
| GWAS | Chinese case-control (31) | |||
| RIPK2 | Receptor-interacting serine/threonine kinase 2 | GWAS | Chinese case-control (20) | Signaling, innate and adaptive immune response; NF-kB inducer |
| Chinese case-control (34) | ||||
| Candidate gene analysis | Vietnamese family-based (25) | |||
| SLC29A3 | Solute carrier family 29 member 3 | GWAS—protein-coding variants | Chinese case-control (21) | Nucleoside transporter |
| TLR1 | Toll-like receptor 1 | GWAS | Indian case-control (24) | Pathogen recognition and activation of innate immunity |
| Candidate gene analysis | Brazilian case-control (44) | |||
| Brazilian family-based (44) | ||||
| TLR2 | Toll-like receptor 2 | Candidate gene analysis | Ethiopian case-control (45) | Pathogen recognition and activation of innate immunity |
| TNFA | Tumor necrosis factor alfa | Candidate-gene analysis | Brazilian family-based and case-control; meta-analysis (46) | Pro-inflammatory cytokine |
| TNFSF8/TNFSF15 | Tumor necrosis factor (Ligand) Superfamily, Member 8/Member 15 | GWAS | Chinese case-control (20) | Pro-inflammatory cytokine |
| Candidate gene analysis | Vietnamese family-based (47) | |||
| Brazilian case-control (47) | ||||
| TYK2 | Tyrosine kinase 2 | GWAS—protein-coding variants | Chinese case-control (21) | Cytokine modulator, interferon signaling pathway |
GWAS, Genome-wide association study; ROS, reactive oxygen species; LPS, lipopolysaccharides; NK, natural killer.