TABLE 1.
Summary of non-HLA leprosy candidate gene association studiesc
| Gene | Reference(s) (yr) | Population | Sample size | Variant(s)a | Phenotype | OR (95% CI), rel. risk, or χ2 value | P valueb |
|---|---|---|---|---|---|---|---|
| CFB (B factor, Bf) | 114 (1980) | Thailand (Chinese) | 24 controls, 38 leprosy | Bf S allele | NE: lep | ||
| Thailand (Thai) | 184 controls, 198 leprosy | Bf S allele | NE: lep | ||||
| 69 (1993) | Brazil | 172 controls, 109 leprosy (73 LL [46 with ENL], 36 non-TL) | Bf F allele (“Bf-F1”) | S: ENL | ND | <0.03 | |
| C2 | 114 (1980) | Thailand Chinese | 24 controls, 38 leprosy | C2 C allele | NE: lep | ||
| Thailand (Thai) | 184 controls, 198 leprosy | C2 C allele | NE: lep | ||||
| C3 | 83 (1972) | Angola | 439 controls, 468 leprosy (97 LL, 180 TL, 191 IL) | S (major allele) vs F (minor allele) | NE: lep or lep type | ||
| 15 (1973) | Angola | 439 controls, 470 leprosy (97 LL, 182 TL, 191 IL) | S (major allele) vs F (minor allele) | NE: lep or lep type | |||
| 4 (1974) | Ethiopia and Mali | 66 controls, 152 leprosy | S (major allele) vs F (minor allele) | S: lep | [OR, 2.33 (0.19-0.98) (dom)] | [0.041] | |
| [OR, 2.43 (0.17-0.98) (het)] | [0.041] | ||||||
| 294 (1975) | Ethiopia | 55 related controls, 91 leprosy | S (major allele) vs F (minor allele) | NE: lep | |||
| C4A | 114 (1980) | Thai and Chinese individuals combined | 123 controls, 201 leprosy (27 TT, 103 BL, 71 LL) | C4A F1 allele (“functionally inactive”) | S: con vs. TT vs BB vs LL (4 × 2 chi square) | χ2 = 13.7 (ND) | <0.01 |
| S: LL vs con | χ2 = 12.6 (ND) | <0.001 | |||||
| C4B | 69 (1993) | Brazil | 172 controls, 109 leprosy (36 non-LL, 73 LL [46 ENL, 27 no ENL]) | C4B*Q0 absent allele | S: lep vs con | ND | 4.4 × 10−5 |
| S: ENL vs no ENL | Rel. risk = 5.3 | [0.017] | |||||
| S: ENL | ND | 3.6 × 10−7 | |||||
| C4B*1 | S: ENL | ND | 3.9 × 10−3 | ||||
| CR1 | 93 (2004) | Malawi | 166-252 controls, 186-399 leprosy (>90% PB) | G3093T | NE: lep | ||
| A4795G “McCoy” | R: lep | OR, 0.3 (0.1-0.8) (rec) | 0.02 | ||||
| G4828A “Swain-Langley” | NE: lep | ||||||
| A4870G | NE: lep | ||||||
| C5507G | NE: lep | ||||||
| DEFB1 (β-defensin 1) | 230 (2009) | Mexico | 151 controls, 75 leprosy | G668C | S: lep | OR, 2.42 (1.37-4.28) (dom) | 0.009 |
| (46 LL) | S: LL vs con | OR, 3.06 (1.47-6.04) (dom) | 0.024 | ||||
| A692G | NE: lep or lep type | ||||||
| A1836G | NE: lep or lep type | ||||||
| Haplotype (668/692/1836) CGA | S: LL | 2.25 (1.23-4.03) | 0.009 | ||||
| FCN2 | 70 (2009) | Brazil, mixed ethnicity | 210 controls, 158 leprosy (92 LL, 14 TT, 22 BL, 27 IL) | 20 SNPs | NE: lep | ||
| Haplotype AGA (−986/−602/−4) | R: lep | OR, 0.13 (0.03-0.43) | <0.013 | ||||
| Haplotype AGAG (−986/−602/−4/+6424) | R: lep | OR, 0.10 (0.11-0.43) | <0.011 | ||||
| IFNG | 248 (2003) | Brazil | 98 controls, 96 leprosy (10 TT, 59 BL, 27 LL) | Intron 1 CA repeat (short [fewer than 122 bp]→long [122-126 bp]) | S: lep | [OR, 2.62 (1.29-5.32)] | 0.01 |
| 93 (2004) | Malawi | 236 controls, 402 cases | Intron 1 T874A | NE: lep | |||
| IL10 | 262 (2002) | Brazil | 62 controls, 202 leprosy (143 MB, 59 PB) | C−819T | S: PB vs MB | OR, 2.28 (1.1-4.5) (allele) | <0.01 |
| S: PB vs con | OR, ↑ [ND] (allele) | <0.05 | |||||
| S: lep | OR, 2.64 (0.93-8.04) (rec) | 0.04 | |||||
| C−592A | NE: lep or lep type | ||||||
| 206 (2004) | Brazil | 283 controls, 297 leprosy (131 PB, 166 MB) | C−819T | NE: lep or lep type | |||
| A−1082G | NE: lep or lep type | ||||||
| C−2763A | NE: lep or lep type | ||||||
| G−2849A | NE: lep or lep type | ||||||
| T−3575A | NE: lep or lep type | ||||||
| Haplotype −3575A/−2849G/−2763C | R: lep | OR, 0.35 (0.13-0.91) | 0.005 | ||||
| R: lep vs PB vs MB | OR, 0.32 (0.12-0.83) (ordinal trait) | 0.006 | |||||
| Haplotype −3575T/−2849A/−2763C | S: lep | OR, 2.37 (1.04-5.39) | 0.027 | ||||
| 93 (2004) | Malawi | 191-215 controls, 349-362 leprosy (>90% PB) | C−819T | NE: lep | |||
| C−592A | NE: lep | ||||||
| A−1082G | NE: lep | ||||||
| 185 (2005) | India | 266 controls, 282 leprosy (144 MB, 142 PB) | C−819T | S: lep | OR, ↑ (ND) (allele) | “Significant” [ND] | |
| S: lep | OR, 2.50 (1.49-4.00) (rec) | <0.001 | |||||
| S: MB vs con | OR, 2.63 (1.51-4.76) (rec) | 0.001 | |||||
| S: PB vs con | OR, 2.32 (1.29-4.16) (rec) | 0.005 | |||||
| C−592A | S: lep | OR, ↑ [ND] (allele) | “Significant” [ND] | ||||
| S: lep | OR, 2.43 (1.47-4.00) (rec) | <0.001 | |||||
| S: MB vs con | OR, 2.56 (1.44-4.54) (rec) | 0.001 | |||||
| S: PB vs con | OR, 2.32 (1.29-4.16) (rec) | 0.005 | |||||
| G−1082A | NE: lep or lep type | ||||||
| C−2763A | NE: lep or lep type | ||||||
| G−2849A | NE: lep or lep type | ||||||
| T−3575A | NE: lep or lep type | ||||||
| Haplotype −3575T/−2849G/−2763C/−1082A/−819C/−592C | R: lep | OR, 0.58 (0.37-0.89) | 0.01 | ||||
| Haplotype −3575T/−2849G/−2763C/−1082A/−819T/−592A | S: MB > PB > con; NE: lep | ND (ordinal trait) | 0.0002 | ||||
| Diplotype of proximal promoter SNPs G−1082A, C−819T, and C−592A (ACC/ACC) | R: lep | [OR, 0.35 (0.19-0.63)] | 0.001 | ||||
| R: MB vs con | [OR, 0.26 (0.11-0.60)] | 0.002 | |||||
| R: PB vs con | [OR, 0.44 (0.22-0.88)] | 0.02 | |||||
| Diplotype of proximal promoter SNPs, G−1082A, C−819T, and C−592A (ATA/ATA) | S: lep | [OR, 1.82 (1.05-3.23)] | 0.03 | ||||
| S: MB vs con | [OR, 1.96 (1.03-3.85)] | 0.04 | |||||
| 225 (2008) | Brazil | 368-380 controls, 321-369 leprosy | C−819T | S: lep | OR, 1.60 (ND) (TT vs CC) | 0.05 | |
| OR, 1.44 (ND) (dom) | 0.026 | ||||||
| A−1082G | ND (not in HWE) | ||||||
| C−2763A | NE: lep | ||||||
| G−2849A | NE: lep | ||||||
| T−3575A | NE: lep | ||||||
| Haplotype −3575T/−2849G/−2763C/−819T | S: lep | OR, 1.35 (ND) | 0.03 | ||||
| 225 (2008) | Meta-analysise | 1,347 controls, 1,355 leprosy | C−819T | S: lep | OR, 1.30 (1.13-1.49) (allele) | 0.0003 | |
| S: lep | OR, 1.28 (1.03-1.60) (dom) | 0.0237 | |||||
| S: lep | OR, 1.66 (1.29-2.15) (rec) | 0.0001 | |||||
| 96 (2009) | Brazil | 240 controls, 156 leprosy | Diplotype G−1082A/C−819T/ C−592C | NE: lep | |||
| IL12B (IL-12p40) | 207 (2007) | India | 89 controls, 80 leprosy | 3′ UTR TaqI site SNP (genotype 2.2 vs 1.1 or 1.2) | R: lep | [OR, 0.13 (0.03-0.58) (rec)] | 0.002 |
| NE: lep type | |||||||
| 14 (2008) | Mexico | 51 controls, 44 LL | 3′ UTR 1188 A/C (TaqI site) | S: lep | [OR, 7.2 (2.38-21.61) (rec)] | <0.05 | |
| IL12RB2 | 218 (2005) | Japan | 68 controls, 176 leprosy (130 LL, 46 TL) | A−1035G | S: LL vs TL | OR, 3.97 (ND) (allele) | <0.001 |
| A−1023G | S: LL vs TL | OR, 2.95 (ND) (allele) | <0.01 | ||||
| −650delG | S: LL vs TL | OR, 3.74 (ND) (allele) | <0.001 | ||||
| A−464G | S: LL vs TL | OR, 3.64 (ND) (allele) | <0.01 | ||||
| Haplotype −1035A/−1023A/−650G/ −464A | R: LL vs TL | ND | 0.0002 | ||||
| R: LL vs con | ND | 0.039 | |||||
| 4 other haplotypes tested | NE: lep or lep type | ||||||
| KIR | 97 (2008) | Brazil | 289 controls, 165 leprosy (65 LL, 49 BB, 42 TT) | KIR2DL1-5 | NE: lep or lep type | ||
| KIR3DL1-3 | NE: lep or lep type | ||||||
| KIR2DS3 | NE: lep type | ||||||
| S: TT vs LL | 2.72 (1.12-6.58) | 0.04 | |||||
| KIR2DS1-2, KIR2DS4-5 | NE: lep or lep type | ||||||
| KIR2DP1 | NE: lep or lep type | ||||||
| KIR3DP1 | NE: lep or lep type | ||||||
| LAMA2 (laminin α-2) | 334 (2002) | Indonesia | 58 controls, 53 leprosy (26 TL, 27 LL) | T7809C | S: TL vs LL | χ2 = 8.07 (genotype) | <0.025 |
| OR, 6.73 (1.94-23.36) (TC vs. TT) | <0.005 | ||||||
| LTA (lymphotoxin-α) | 93 (2004) | Malawi | 333 controls, 184 leprosy (85% PB) | 5′ UTR microsatellite (AC/GT)n at −3.5-kb 105-bp allele | S: lep | OR, 1.6 (1.1-2.4) | 0.03 |
| 5′ UTR microsatellite (AC/GT)n at −3.5-kb 101-bp allele | S: MB vs con | χ2 = 11.7 (ND) | 0.003 | ||||
| 8 (2007) | India | 371 controls, 364 leprosy | LTA−294 univariate analysis | S: lep | 1.78 (1.29-2.45) | 0.0004 | |
| LTA−294 multivariate analysis | NE: lep | ||||||
| LTA−293 | NE: lep | ||||||
| LTA+10 | NE: lep | ||||||
| LTA+80 (A allele) univariate analysis | NE: lep | ||||||
| LTA+80 (A allele) multivariate analysis | S: lep | 1.60 (1.10-2.33) (dom) | 0.01 | ||||
| LTA+80 (A allele) subgroup ages 16-25 yr | S: lep | 2.95 (1.32-6.58) (dom) | 0.006 | ||||
| LTA+252 | NE: lep | ||||||
| LTA+368 | NE: lep | ||||||
| MCCD1 rs2259435 (A allele) univariate analysis | S: lep | 1.59 (1.24-2.04) | 0.0002 | ||||
| MCCD1 rs2259435 (A allele) multivariate analysis | S: lep | 1.82 (1.38-2.41) | 0.0004 | ||||
| Vietnamd | 194 simplex leprosy families | LTA−294 | NE: lep | ||||
| LTA−293 univariate analysis | S: lep | 1.97 (1.30-2.99) | 0.0009 | ||||
| LTA−293 multivariate analysis | S: lep | 1.97 (1.30-2.99) | 0.0009 | ||||
| LTA+10 | NE: lep | ||||||
| LTA+80 univariate analysis | S: lep | 1.74 (1.16-2.60) | 0.007 | ||||
| LTA+252 | NE: lep | ||||||
| LTA+368 univariate analysis | S: lep | 1.63 (1.09-2.43) | 0.02 | ||||
| Brazil | 192 controls, 209 leprosy | LTA−294 | NE: lep | ||||
| LTA−293 | NE: lep | ||||||
| LTA+10 | NE: lep | ||||||
| LTA+80 (A allele) | NE: lep | ||||||
| LTA+80 (A allele) subgroup ages 16-25 yr | Trend: lep | 2.76 (0.74-10.32) | NS [ND] | ||||
| LTA+252 | NE: lep | ||||||
| LTA+368 | NE: lep | ||||||
| LTA4H | 304 (2010) | Nepal | 899 leprosy (443 MB without ENL, 335 PB) | rs1978331 T/C | R: MB vs PB | OR, 0.62 (0.46-0.82) (het) | 0.001 |
| rs2660898 T/G | R: MB vs PB | OR, 0.70 (0.52-0.95) (het) | 0.021 | ||||
| MBL2 | 93 (2004) | Malawi | 261 controls, 231 leprosy | G239A | NE: lep | ||
| 71 (2007) | Brazil | 214 controls, 264 leprosy (150 LL, 36 TL, 37 BL, 17 IL) | Haplotype LYPA (−550L/221Y/+4P/exon 1 A) | S: lep | OR, 2.25 (1.31-3.88) | 0.020 | |
| S: LL vs con | OR, 2.22 (1.21-4.05) | 0.060 | |||||
| S: BL vs con | OR, 2.98 (1.29-6.87) | 0.060 | |||||
| “Low”-MBL-producing genotypes | R: LL vs TL | OR, 0.31 (0.13-0.71) | 0.012 | ||||
| MICA/MICB | 331 (1999) | China | 112 controls, 69 leprosy | MICA-A5 | R: lep | Rel. risk, 0.62 (allele) | 0.06 |
| R: MB vs con | Rel. risk, 0.56 (allele) | <0.05 | |||||
| Haplotype MICA-A5 with HLA-B46 | R: lep | Rel. risk, 0.37 | <0.03 | ||||
| R: MB vs con | Rel. risk, 0.22 | <0.01 | |||||
| MRC1 | 12 (2010) | Vietnamd | 490 simplex families (53% MB) + 90 multiplex families (55% MB) for a total of 704 leprosy patients (325 PB, 374 MB) | rs1926736 G/A A allele (396S) | R: lep | OR: 0.76 (0.60-0.96) (best dom) | 0.035 |
| R: MB | OR: 0.71 (0.51-0.99) (best dom) | 0.034 | |||||
| Brazil | 384 leprosy (∼162 MB, ∼167 PB), 399 controls, | rs1926736 A/G G allele (396G) | S: lep | OR, 1.34 (1.06-1.70) (additive) | 0.016 | ||
| S: MB | OR, 1.42 (1.05-1.93) (additive) | 0.023 | |||||
| rs2437257 C/G (407L) | NE: lep | ||||||
| R: MB | OR, 0.63 (0.41-0.97) (dom) | 0.04 | |||||
| Haplotype G396-F407 | S: lep | OR, 1.41 (1.13-1.76) | 0.003 | ||||
| S: MB | OR, 1.61 (1.21-2.14) | 0.001 | |||||
| Haplotype S396-F407 | R: lep | OR, 0.75 (0.59-0.95) | 0.019 | ||||
| R: MB | OR, 0.68 (0.50-0.93) | 0.015 | |||||
| NOD2 | 93 (2004) | Malawi | ND | C802T | Not present in population | ||
| C2104T | |||||||
| G2722C | |||||||
| 3020insC 1007fs | |||||||
| 27 (2010) | Nepal | 101 controls, 933 leprosy | rs12448797 T/C (C allele) | S: lep | OR, 2.18 (1.06-5.23) (allele) | 0.031 | |
| OR, 2.47 (1.12-6.44) (dom) | 0.021 | ||||||
| rs2287195 A/G (G allele) | S: lep | OR, 1.51 (1.08-2.14) (allele) | 0.013 | ||||
| OR, 1.85 (1.19-2.88) (dom) | 0.004 | ||||||
| rs8044354 A/G (G allele) | S: lep | OR, 1.53 (1.11-2.10) (allele) | 0.006 | ||||
| OR, 2.07 (1.33-3.22) (dom) | 0.0006 | ||||||
| rs13339578 G/A (A allele) | S: lep | OR, 1.71 (1.10-2.68) (dom) | 0.012 | ||||
| rs4785225 C/G (G allele) | S: lep | OR, 1.67 (1.07-2.60) (dom) | 0.017 | ||||
| rs751271 A/C (C allele) | S: lep | OR, 1.65 (1.07-2.58) (dom) | 0.016 | ||||
| rs1477176 T/C (C allele) | R: lep | OR, 0.44 (0.28-0.71) (allele) | <0.001 | ||||
| OR, 0.43 (0.26-0.73) (dom) | 0.0005 | ||||||
| 124 ENL | rs2287195 A/G (G Allele) | S: ENL vs no ENL | OR, 1.82 (1.12-3.00) (dom) | 0.011 | |||
| 428 no ENL | rs8044354 A/G (G Allele) | S: ENL vs no ENL | OR, 1.34 (0.99-1.82) (allele) | 0.046 | |||
| OR, 2.17 (1.26-3.88) (dom) | 0.003 | ||||||
| rs7194886 C/T (T allele) | S: ENL vs no ENL | OR, 1.66 (1.07-2.57) (dom) | 0.016 | ||||
| rs6500328 A/G (G allele) | S: ENL vs no ENL | OR, 1.69 (1.09-2.62) (dom) | 0.012 | ||||
| rs17312836 A/C (C allele) | S: ENL vs no ENL | OR, 1.43 (1.00-2.04) (allele) | 0.039 | ||||
| OR, 1.70 (1.09-2.64) (dom) | 0.013 | ||||||
| rs1861759 A/C (C allele) | S: ENL vs no ENL | OR, 1.42 (1.00-2.01) (allele) | 0.037 | ||||
| OR, 1.78 (1.15-2.73) (dom) | 0.006 | ||||||
| rs1861758 C/T (T allele) | S: ENL vs no ENL | OR, 1.41 (0.99-1.99) (allele) | 0.047 | ||||
| OR, 1.69 (1.09-2.63) (dom) | 0.014 | ||||||
| 240 RR | rs2287195 A/G (G allele) | R: RR vs no RR | OR, 0.74 (0.58-0.95) (allele) | 0.013 | |||
| 693 no RR | OR, 0.69 (0.50-0.96) (dom) | 0.023 | |||||
| rs8044354 A/G (G allele) | R: RR vs no RR | OR, 0.74 (0.59-0.92) (allele) | 0.005 | ||||
| OR, 0.69 (0.49-0.96) (dom) | 0.021 | ||||||
| rs8043770 C/G (G allele) | R: RR vs no RR | OR, 0.73 (0.57-0.94) (allele) | 0.012 | ||||
| OR, 0.67 (0.49-0.92) (dom) | 0.010 | ||||||
| rs7194886 C/T (T allele) | R: RR vs no RR | OR, 0.74 (0.55-0.98) (allele) | 0.032 | ||||
| OR, 0.69 (0.49-0.96) (dom) | 0.023 | ||||||
| rs1861759 A/C (C allele) | R: RR vs no RR | OR, 0.75 (0.57-0.99) (allele) | 0.041 | ||||
| OR, 0.69 (0.49-0.95) (dom) | 0.019 | ||||||
| rs4785225 C/G (G allele) | R: RR vs no RR | OR, 0.71 (0.52-0.97) (dom) | 0.027 | ||||
| rs751271 A/C (C allele) | R: RR vs no RR | OR, 0.73 (0.53-0.99) (dom) | 0.038 | ||||
| PARK2/PACRG | 196 (2004) | Brazil | 388 controls, 587 leprosy (38% PB, 62% MB) | rs2803104 (A allele) | NE: lep | ||
| 10 kb_target_5_2 (T allele) | S: lep | ND | 0.019 | ||||
| PARK2_e01(−697) (G allele) | S: lep | ND | 0.001 | ||||
| PARK2_e01(−2599) (T allele) | S: lep | ND | 0.003 | ||||
| PARK2_e01(−3024) (C allele) | NE: lep | ||||||
| PARK2_e01(−3800) (G allele) | S: lep | ND | 0.009 | ||||
| 28 kb_target_2_1 (T allele) | NE: lep | ||||||
| 28 kb_target_4_1 (A allele) | S: lep | ND | 0.003 | ||||
| rs1514343 (T allele) | S: lep | ND | 0.045 | ||||
| rs1333955 (C allele) | S: lep | ND | 0.034 | ||||
| rs1040079 (C allele) | S: lep | ND | 0.001 | ||||
| 40 kb_target_8_F60 (A allele) | S: lep | ND | 0.032 | ||||
| 40 kb_target_8_F706 (G allele) | NE: lep | ||||||
| 184 (2006) | India | 350 controls, 286 leprosy (144 MB, 142 PB) | PARK2_e01(−2599) | NE: lep or lep type | |||
| PARK2_e01(−697) | NE: lep or lep type | ||||||
| 28 kb_target_2_1 | NE: lep or lep type | ||||||
| 10 kb_target_5_2 | NE: lep or lep type | ||||||
| rs1040079 | NE: lep or lep type | ||||||
| SLC11A1 (NRAMP) | 256 (1999) | India | 165 controls, 227 leprosy (105 TL, 122 LL) | 5′ MS [(GT)n or (CA)n] | NE: lep or lep type | ||
| 3′ UTR TGTG del/ins | NE: lep or lep type | ||||||
| (469 + 14 G/C) intron 4 SNP | NE: lep or lep type | ||||||
| Exon 2 polymorphism | NE: lep or lep type | ||||||
| 191 (2001) | Mali | 201 controls, 273 leprosy (92 PB, 181 MB) | 3′ UTR TGTG deletion | S: MB vs PB (het vs del/del) | OR, 5.79 (1.46-24.61) | 0.003 | |
| 89 (2004) | Brazil | 61 controls (30 positive for MR, 24 negative for MR), 90 leprosy (45 MB, 45 PB, 18 positive for MR, 64 negative for MR) | Alleles of 5′ promoter microsatellite [(GT)n or (CA)n] polymorphisms | NE: lep, lep type, MR | |||
| 321 (2007) | Thailand | 140 controls, 37 leprosy (13 PB, 24 MB) | (469 + 14 G/C) intron 4 SNP | NE: lep or lep type | |||
| D543N SNP | NE: lep or lep type | ||||||
| 3′ UTR TGTG del/ins | NE: lep or lep type | ||||||
| 93 (2004) | Malawi | 283-429 controls, 244-258 leprosy (>90% PB) | Promoter microsatellite(GT)n genotypes 199/201, 199/199, 201/201 | NE: lep | |||
| Other promoter microsatellite(GT)n genotypes | NE: lep | ||||||
| Exon 2, 9-bp del | NE: lep | ||||||
| 3′ UTR TGTG del/ins | NE: lep | ||||||
| 3′ UTR CAAA del/ins | NE: lep | ||||||
| TLR1 | 149 (2007) | Turkey | 90 controls, 57 leprosy | T1805G G allele (602S) | R: lep | OR, 0.48 (0.29-0.80) | 0.004 |
| T1805G GG genotype (602SS) | R: lep | ND | 0.02 | ||||
| 198 (2008) | Nepal | 933 leprosy (311 TL, 490 LL) | T1805G G allele (602S) | NE: lep | |||
| NE: TL vs LL | |||||||
| R: RR | OR, 0.51 (0.29-0.87) (allele) | 0.01 | |||||
| 271 (2009) | Bangladesh | 543 controls, 842 leprosy (702 PB, 140 MB) | T1805G G allele (602S) | NE: lep | |||
| A743G GG genotype (248SS) | S: lep | OR, 1.34 (1.06-1.70) (rec) | [0.016] | ||||
| A743G G allele (248S) | R: ENL | OR, 0.40 (0.16-0.99) (allele) | [0.04] | ||||
| A743G GG genotype (248SS) | Trend: RR | OR, 1.57 (0.97-2.55) (rec) | NS | ||||
| TLR2 | 93 (2004) | Malawi | 379 controls, 210 cases (26 MB, 184 PB) | Intron 2 microsatellites 216 bp, 222 bp, 224 bp, 226 bp | NE: lep | ||
| Intron 2 microsatellite 224 bp | MB vs PB | χ2= 6.3 (ND) | 0.042 | ||||
| 35 (2008) | Ethiopia | 197 controls, 441 leprosy (298 LL, 138 TL, 5 uncharacterized, 66 RR, 150 no RR) | Microsatellite (280 bp) | S: RR | OR, 5.83 (1.98-17.15) (rec) | 0.001 | |
| Microsatellite (288 bp) | R: LL vs. TL | OR, 0.49 (0.27-0.90) (dom) | 0.02 | ||||
| Microsatellite (290 bp) | R: lep | OR, 0.62 (0.41-0.93) (additive) | 0.02 | ||||
| Other microsatellites | NE: lep, lep type, RR | ||||||
| C597T (N199N) | R: RR | OR, 0.34 (0.17-0.68) (dom) | 0.002 | ||||
| T1350C (S450S) | NE: lep, lep type, RR | ||||||
| “280 C-T haplotype” (280 bp, 297C, 1350T) | S: RR | OR, 6.39 (2.14-19.07) (rec) | 0.001 | ||||
| TLR4 | 36 (2009) | Ethiopia | 197 controls, 441 leprosy (298 lepromatous [199 BL, 81 LL, 18 MB], 138 tuberculoid [128 BT, 3 TT, 7 PB], 5 uncharacterized, 133 neuritis, 66 RR, 17 ENL) | G896A | R: lep | OR, 0.34 (0.20-0.57) (additive) | <0.001 |
| T1196C | R: lep | OR, 0.15 (0.06-0.39) (dom) | <0.001 | ||||
| G1530T | R: lep | OR, 0.38 (0.14-1.01) (dom) | 0.05 | ||||
| A1976G | NE: lep or lep type | ||||||
| Haplotype 896G/1196T/1530G/1976A | R: lep | OR, 0.12 (0.05-0.34) | <0.001 | ||||
| Haplotype 896G/1196C/1530T/1976A | R: lep | OR, 0.23 (0.08-0.69) | 0.008 | ||||
| 93 (2004) | Malawi | 288 controls, 235 leprosy | G896A | NE: lep | |||
| TNF | 257 (1997) | India | 160 controls, 228 leprosy (121 LL, 107 TT) | G−308A | S: LL vs con | Rel. risk, 2.5 (1.1-6.5) (allele) | 0.03 |
| 261, 262 (2000 and 2002, respectively) | Brazil | 92 controls, 300 leprosy (MB [70 LL, 85 BL, 55 BB], PB [63 BT, 2 TT], 10 indeterminant, 15 pure neuritis) | G−308A | R: lep | [OR, 0.63 (0.39-1.0) (allele)] | <0.05 | |
| R: MB vs con | [OR, 0.53 (0.30-0.91) (allele)] | <0.01 | |||||
| S: PB vs MB | OR, 1.65 (0.9-2.9) (allele) | <0.05 | |||||
| G−238A | NE: lep or lep type | ||||||
| 93 (2004) | Malawi | 258-283 controls, 216-243 leprosy (>90% PB) | G−238A | NE: lep | |||
| G−308A | NE: lep | ||||||
| G−376A | NE: lep | ||||||
| C−863A | NE: lep | ||||||
| 321 (2007) | Thailand | 140 controls, 37 leprosy (13 PB, 24 MB) | G−308A | S: MB vs con (het) | OR, 2.69 (ND) | 0.04 | |
| G−238A | NE: lep or lep type | ||||||
| VDR | 256 (1999) | India | 166 controls, 231 leprosy (107 TL, 124 LL) | TaqI T→C (“T”→“t”) | S: TL vs con | OR, 3.22 (1.47-7.13) (rec) | 0.001 |
| R: LL vs con | [OR, 0.60 (0.37-0.96) (dom)] | [0.03] | |||||
| [OR, 0.54 (0.33-0.86) (het)] | [0.01] | ||||||
| 93 (2004) | Malawi | 328-398 controls, 168-247 leprosy (>90% PB) | TaqI T→C (“T”→“t”) | Controls violate HWE | |||
| ApaI G→T (“a”→“A”) | NE: lep | ||||||
| BsmI C→T (“b”→“B”) | NE: lep | ||||||
| 113 (2006) | Brazil | 68 controls, 102 leprosy (55 PB, 47 MB) | TaqI T→C (“T”→“t”) genotypes alone | NE: lep or lep type | |||
| 85 (2009) | Mexico | 144 controls, 71 LL | TaqI T→C (“T”→“t”) | R: lep (LL) | OR, 0.55 (0.31-0.98) (dom) | 0.04 | |
| [OR, 0.50 (0.27-0.92) (het)] | [0.03] |
a
By convention, the variant SNP (a) is designated second (e.g., “A→a,” “A/a,” or “A[nucleotide position]a”).
b
When present, corrected P values are reported.
c
Abbreviations: con, controls, lep, leprosy (multiple forms or unspecified forms); MB, multibacillary; PB, paucibacillary; BL, borderline (depending on the study, this may indicate BB, BL, BT, or any combination of these); IL, indeterminate leprosy; LL, lepromatous leprosy (depending on study, this may indicate LL only or LL plus BL or plus BB); TL, tuberculoid leprosy (depending on the study, this may indicate TT or TT plus BT); ENL, erythema nodosum leprosum; RR, reversal reaction; MR, Mitsuda reaction; S, susceptible; R, resistant; dom, dominant model of genetic analysis (compares aa plus Aa versus AA); rec, recessive genetic model (compares aa versus AA plus Aa); het, heterozygotes or heterozygous model of analysis (Aa versus AA plus aa); HWE, Hardy-Weinberg equilibrium; del, deletion; ins, insertion; ND, no data (data not shown or not available); NE, no effect (no association found); NE: lep or lep type, phenotypes investigated and relevant variant not associated with either phenotype (i.e., not with leprosy overall or a specific type of leprosy, such as MB, PB, TT, or LL); NS, not significant; rel risk, relative risk. Data in brackets indicate where P values, ORs, or 95% confidence intervals were calculated by these reviewers or where ORs have been inverted to simplify comparison of the same risk allele across different studies.
d
The Vietnamese component of this study was a family-based association study.