Table 3 Genetic variation associated with DENV disease. We include in this table all variants studied by two or more research groups and variants found to have a significant association by one research group
Gene | Genetic Variation | Entrez Gene ID [31] | Major Allele | Minor Allele | Number of Cases | Number in Comparison Group | Country | Key Results | Meta-Analyzed |
|---|---|---|---|---|---|---|---|---|---|
BAK1 | rs5745568 | 578 | G | T | 509 DHF/DSS | 409 DF | Thailand | 1.32 (1.09–1.60) odds of severe disease associated with G allele [67] | No |
CCR5 | rs333 | 1234 | – | Δ32 deletion | 56 DF | 91 controls | Australia | No significant association with disease [68] | Yes |
88 DHF/DSS | 335 controls | Brazil | No significant association with disease [69] | ||||||
CD209/ DCSIGN | rs480803 | 30,835 | A | G | 509 DHF/DSS | 409 DF | Thailand | No significant association with disease [67] | Yes |
A | G | 88 DHF/DSS | 335 controls | Brazil | No significant association with disease [69] | ||||
A | G | 112 symptomatic | 104 controls | India | No significant association with disease [70] | ||||
A | G | 103 symptomatic | 145 asymptomatic infections | Mexico | No significant association with disease [71] | ||||
A | G | 156 DF and 12 DHF | 72 controls | Brazil | No significant association with disease [72] | ||||
A | G | 606 symptomatic | 696 controls | Thailand | 5.84 (2.77–12.31) odds of DHF compared to DF and 0.204 (P = 2.0 × 10− 6) odds of symptomatic infection compared to controls [73] | ||||
A | G | 286 symptomatic | 236 asymptomatic infections | Brazil | No significant association with disease [74] | ||||
A | G | 176 DF and 135 DH0046 | 120 controls | Taiwan | 2.36 (1.12–4.97) odds of symptomatic infection compared to controls, 3.68 (1.67–8.09) odds of DHF compared to controls, and 2.46 (1.32–4.59) odds of DHF compared to DF [75] | ||||
CFH | rs3753394 | 3075 | C | T | 187 DHF | 121 DF | Thailand | No significant association with disease [76] | Noa |
|  |  |  | C | T | 87 DHF | 34 DF | Brazil | 2.53 (1.38–4.69) odds of severe disease compared to mild disease under dominant model [77] |  |
CLEC5A | rs1285933 | 23,601 | T | C | 88 DHF/DSS | 335 controls | Brazil | 2.25 (1.07–4.87) odds of severe disease for TT compared to CC genotype [69] | No |
CXCL8/ IL8 | rs4973 | 3576 | T | A | 45 DHF | 108 controls | India | 0.43 (0.20–0.93) odds of severe disease [78] | No |
DDX58 | rs3205166 | 23,586 | T | G | 120 DENV positive | 109 controls | India | 0.66 odds of disease associated with G allele for rs3205166 [79] | No |
rs11795343 | |||||||||
rs669260 | |||||||||
FCγRII-α | rs1801274 | 2212 | A (H amino acid) | G (R amino acid) | 103 symptomatic | 145 asymptomatic infections | Mexico | 0.51 (0.26–0.98) odds of symptomatic infection and 0.45 (0.21–0.96) odds of severe disease compared to controls [71] | Yes |
T (H) | C (R) | 89 DF and 33 DHF | 107 controls | India | No significant association with disease [80] | ||||
T (H) | C (R) | 68 DF, 29 DHF/DSS | 42 asymptomatic infections | Cuba | 10.56 (2.33–54.64) odds of DHF compared to asymptomatic disease for under dominant model [81] | ||||
T (H) | C (R) | 302 DHF | 238 controls | Vietnam | No significant association with disease [82] | ||||
T (H) | C (R) | 40 DF, 30 DHF/DSS | 40 asymptomatic infections | Pakistan | 3.21 (1.29–7.97) odds of symptomatic disease, 2.82 (1.00–7.97) odds of DF, and 3.90 (1.13–13.07) odds of DHF/DSS over asymptomatic infection [83] | ||||
HPA | HPA 1a/1a | Not available | 1a antigen | 1b antigen | 75 DHF | 90 DF | India | 1.93 odds (p = 0.006) of severe disease [84] | No |
HPA 2a/2b | 2a antigen | 2b antigen | 75 DHF | 90 DF | India | 2.8 odds (p = 0.007) of severe disease [84] | No | ||
IFN-γ | rs2430561 | 3458 | A | T | 80 symptomatic | 100 DEN-negative febrile cases and 99 healthy controls | Brazil | 2.23 (p = 0.0255) odds compared to DEN-negative and 2.37 (p = 0.0165) odds compared to controls [85] | Yes |
A | T | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | ||||
A | T | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
IL-1B | rs16944 | 3553 | A | G | 45 DHF | 108 controls | India | No significant association with disease [78] | Yes |
C | T | 118 symptomatic | 80 controls | Brazil | No significant association with disease [88] | ||||
rs1143627 | C | T | 367 secondary DHF and 74 secondary DSS | 313 secondary DF | Thailand | 3.49 (1.36–8.95) odds of DSS compared to DHF and 2.81 (1.12–7.06) odds of DSS compared to DF under dominant models [89] | No | ||
IL-1RA | 86 base pair tandem repeat | 3557 | 4 repeats | 2 repeats | 367 secondary DHF and 74 secondary DSS | 313 secondary DF | Thailand | 1.86 (1.05–3.26) odds of DSS compared to DHF and 1.86 (1.05–3.27) odds of DSS compared to DF for the 2/4 genotype [89] | Noa |
1 repeat | 2–4 repeats | 280 DHF | 229 controls | Vietnam | No significant association between IL-1RA repeats and DHF [82] | ||||
IL-6 | rs1800795 | 3569 | G | C | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | Yes |
G | C | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
G | C | 118 symptomatic | 80 controls | Brazil | No significant association with disease [88] | ||||
G | C | 200 DF | 309 controls | Brazil | 0.62 (0.42–0.91) odds of disease among heterozygotes compared to homozygote wild-type [90] | ||||
IL-10 | rs1800871 | 3586 | C | T | 88 DSS | 335 controls | Brazil | No significant association with disease [69] | Yes |
A | G | 45 DHF | 108 controls | India | No significant association with disease [78] | ||||
C | T | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | ||||
C | T | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
C | T | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
T | C | 86 DF, 182 DHF, 14 DSS | 120 controls | Malaysia | No significant association with disease [91] | ||||
C | T | 107 DHF | 62 controls | Sri Lanka | No significant association with disease [92] | ||||
rs1800872 | C | A | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | Yes | ||
C | A | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
C | A | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
A | C | 86 DF, 182 DHF, 14 DSS | 120 controls | Malaysia | No significant association with disease [91] | ||||
A | C | 107 DHF | 62 controls | Sri Lanka | No significant association with disease [92] | ||||
rs1800896 | A | G | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | Yes | ||
A | G | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
A | G | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
A | G | 86 DF, 182 DHF, 14 DSS | 120 controls | Malaysia | No significant association with disease [91] | ||||
A | G | 107 DHF | 62 controls | Sri Lanka | No significant association with disease [92] | ||||
JAK1 | rs11208534 | 3716 | T | C | 50 DHF | 236 DF | Brazil | 4.20 (1.7–10.4) odds of severe disease [74] | No |
rs2780831 | G | A | 50 DHF | 236 DF | Brazil | 2.1 (1.1–4.1) odds of severe disease [74] | No | ||
rs310196 | T | G | 50 DHF | 236 DF | Brazil | 0.4 (0.2–0.7) odds of severe disease [74] | No | ||
MBL2 | Exon 1 | 4153 | A | O | 110 symptomatic | 150 controls | Brazil | No significant association with disease [93] | Yes |
A | O | 57 DHF | 104 DF | Brazil | 7.24 (1.38–38.02) odds of DHF among OO genotype compared to AA genotype [94] | ||||
MICB | rs3132468 | 4277 | T | C | 76 DSS | 409 DF, 432 DHF | Thailand | 1.58 (1.02–2.40) odds of DSS compared to non-DSS [95] | Yes |
T | C | 2008 DSS | 2018 controls | Vietnam | 1.34 (1.23–1.46) odds of DSS per allele [96] | ||||
T | C | 3961 cases | 1068 controls | Vietnam | 1.42 (1.20–1.64) odds of DSS per allele [97] | ||||
PLCE1 | rs3740360 | 51,196 | A | C | 2008 DSS | 2018 controls | Vietnam | 0.80 (0.75–0.86) odds per allele of DSS [96] | Yes |
A | C | 3961 cases | 1068 controls | Vietnam | 0.77 (0.59–0.99) odds per allele of DSS [97] | ||||
rs3765524 | C | T | 76 DSS | 409 DF, 432 DHF | Thailand | 1.49 (1.00–2.26) odds of DSS compared to non-DSS [95] | Yes | ||
C | T | 2008 DSS | 2018 controls | Vietnam | 0.80 (0.75–0.86) odds per allele of DSS [96] | ||||
RXRA | rs12339163 | 6256 | G | A | 60 DHF | 137 asymptomatic infections and controls | Cuba | 0.36 (0.17–0.77) odds of severe disease [98] | No |
rs3118593 | A | C | 60 DHF | 137 asymptomatic infections and controls | Cuba | 0.44 (0.25–0.77) odds of severe disease [98] | |||
rs4262378 | G | A | 60 DHF | 137 asymptomatic infections and controls | Cuba | 0.41 (0.24–0.72) odds of severe disease [98] | |||
rs4424343 | A | G | 60 DHF | 137 asymptomatic infections and controls | Cuba | 0.43 [0.24–0.76] odds of severe disease [98] | |||
rs62576287 | C | A | 60 DHF | 137 asymptomatic infections and controls | Cuba | 0.10 (0.01–0.83) odds of severe disease [98] | |||
TAP1 | amino acid 333 | 6890 | Ile | Val | 90 DF, 75 DHF, 32 DSS | 100 controls | India | 2.58 (p = 0.007) odds of DHF among heterozygotes compared to DF [84] | Yes |
Ile | Val | 107 DHF | 62 controls | Sri Lanka | No significant association with disease [92] | ||||
TAP2 | amino acid 379 | 6891 | Val | Ile | 107 DHF | 62 controls | Sri Lanka | No significant association with disease [92] | Yes |
Val | Ile | 90 DF, 75 DHF, 32 DSS | 100 controls | India | 2.11 (p = 0.001) odds of DHF among heterozygotes [99] | ||||
TGFβ1 | rs1800471 | 7040 | G | C | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] |  |
G | C | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
rs1982073 | T | C | 25 DHF | 41 DF | Venezuela | No significant association with disease [86] | Yes | ||
T | C | 43 DHF | 99 controls | Cuba | No significant association with disease [87] | ||||
T | C | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
TIRAP | rs8177374 | 114,609 | C | T | 33 DHF | 109 controls | India | 2.64 (1.17–5.99) odds of severe disease among heterozygotes [100] | No |
TLR3 | rs3775291 | 7098 | C | T | 33 DHF | 87 DF | India | 0.39 (0.16–0.88) odds of severe disease associated with T allele [100] | No |
TNF-α | rs361525 | 7124 | G | A | 86 DF, 182 DHF, 14 DSS | 120 controls | Malaysia | 4.92 (1.10–21.90) odds of DHF compared to control group for heterozygotes [91] | Yes |
G | A | 41 DF, 32 DHF | 169 controls | Mexico | 0.19 (0.02–0.78) odds of disease with A allele [101] | ||||
rs1800629 | G | A | 80 symptomatic | 100 DEN-negative febrile cases and 99 healthy controls | Brazil | No significant association with disease [85] | Yes | ||
G | A | 25 DHF | 41 DF | Venezuela | 2.5 (1.47–4.13) odds of severe disease [86] | ||||
G | A | 43 DHF | 99 controls | Cuba | 3.51 (1.77–7.00) odds of severe disease [87] | ||||
G | A | 200 DF | 309 controls | Brazil | No significant association with disease [90] | ||||
G | A | 86 DF, 182 DHF, 14 DSS | 120 controls | Malaysia | 0.43 (0.22–0.84) odds of DHF compared to control for heterozygotes [91] | ||||
G | A | 107 DHF | 62 controls | Sri Lanka | 2.53 (1.10–5.83) odds of disease for GG genotype [92] | ||||
G | A | 85 DF, 29 DHF | 110 controls | India | No significant association with disease [102] | ||||
G | A | 19 DF, 82 DHF | 106 controls | Thailand | No significant association with disease [103] | ||||
G | A | 85 DF, 45 DHF | 163 controls | Mexico | No significant association with disease [101] | ||||
TLR4 | amino acids 299 and 399 | 7099 | Asp299, Thr399 | Gly299, Ile399 | 201 DHF | 179 controls | Indonesia | No significant association with disease [104] | Yes |
Asp299, Thr399 | Gly299, Ile399 | 63 DF, 57 DHF/DSS | 200 controls | India | 2.00 (1.17–3.43) odds associated with Gly299 for DF versus controls, and 2.38 (1.16–4.85) associated with Ile399 for DF versus controls [105] | ||||
VDR | rs731236 | 7421 | T | C | 302 DHF | 238 controls | Vietnam | Associated with more severe disease (p = 0.033) [82] | Yes |
T | C | 83 DF, 29 DHF | 105 controls | India | No significant association with disease [106] |