Table III.
Associations between miRNA-SNPs and AIDS-NHL risk in the Multicenter AIDS Cohort Study
| Overall AIDS-NHL | Systemic AIDS-NHL | CNS AIDS-NHL | |||||
|---|---|---|---|---|---|---|---|
| Ca/Coa | OR (95% CI)b | Ca/Coa | OR (95% CI)b | Ca/Coa | OR (95% CI)b | ||
| microRNA coding regions | |||||||
| miR-196a2 rs11614913 | CC | 72/196 | 1.00 (Ref) | 41/138 | 1.00 (Ref) | 31/58 | 1.00 (Ref) |
| CT | 88/257 | 0.91 (0.63–1.31) | 67/169 | 1.19 (0.76–1.86) | 21/88 | 0.52 (0.27–0.99)c | |
| TT | 19/76 | 0.63 (0.36–1.10) | 14/58 | 0.69 (0.36–1.32) | 5/18 | 0.72 (0.30–1.75) | |
| Log-Add | 179/529 | 0.80 (0.62–1.05) | 122/365 | 0.89 (0.65–1.23) | 57/164 | 0.62 (0.37–1.02) | |
| miR-26a1 rs7372209 | CC | 94/276 | 1.00 (Ref) | 61/180 | 1.00 (Ref) | 33/96 | 1.00 (Ref) |
| CT | 77/215 | 1.25 (0.87–1.81) | 56/155 | 1.27 (0.83–1.96) | 21/60 | 1.35 (0.71–2.56) | |
| TT | 9/38 | 0.84 (0.42–4.67) | 6/30 | 0.78 (0.36–1.69) | 3/8 | 1.16 (0.40–3.40) | |
| Log-Add | 180/529 | 1.06 (0.79–1.42) | 123/365 | 1.03 (0.74–1.45) | 57/164 | 1.31 (0.74–2.32) | |
| miR-27a rs895819 | TT | 67/242 | 1.00 (Ref) | 50/170 | 1.00 (Ref) | 17/72 | 1.00 (Ref) |
| TC | 92/242 | 1.23 (0.84–1.82) | 58/162 | 1.12 (0.71–1.75) | 34/80 | 1.41 (0.71–2.78) | |
| CC | 21/43 | 1.56 (0.85–2.85) | 15/32 | 1.41 (0.70–2.85) | 6/11 | 1.51 (0.60–3.77) | |
| Log-Add | 180/527 | 1.29 (0.97–1.73) | 123/364 | 1.21 (0.85–1.73) | 57/163 | 1.45 (0.87–2.40) | |
| miR-300 rs12894467 | CC | 58/183 | 1.00 (Ref) | 38/114 | 1.00 (Ref) | 20/69 | 1.00 (Ref) |
| CT | 85/265 | 0.99 (0.66–1.48) | 57/198 | 0.83 (0.51–1.34) | 28/67 | 1.29 (0.66–2.53) | |
| TT | 37/80 | 1.31 (0.79–2.17) | 28/52 | 1.40 (0.78–2.52) | 9/28 | 1.09 (0.47–2.55) | |
| Log-Add | 180/528 | 1.14 (0.87–1.49) | 123/364 | 1.16 (0.84–1.60) | 57/164 | 1.14 (0.70–1.85) | |
| pre-miR-146a rs2910164 | GG | 110/314 | 1.00 (Ref) | 72/204 | 1.00 (Ref) | 38/110 | 1.00 (Ref) |
| GC | 62/193 | 0.98 (0.67–1.43) | 45/145 | 0.98 (0.63–1.53) | 17/48 | 1.03 (0.54–1.97) | |
| CC | 8/22 | 0.93 (0.44–1.97) | 6/16 | 0.96 (0.42–2.18) | 2/6 | 1.12 (0.35–3.55) | |
| Log-Add | 180/529 | 0.97 (0.71–1.32) | 123/365 | 0.97 (0.68–1.40) | 57/164 | 1.08 (0.60–1.94) | |
| Functional SNPs in miRNA biogenesis genes | |||||||
| AGO2 rs4961280 | CC | 117/348 | 1.00 (Ref) | 75/241 | 1.00 (Ref) | 42/107 | 1.00 (Ref) |
| CA | 56/167 | 1.00 (0.68–1.49) | 43/114 | 1.23 (0.77–1.97) | 13/53 | 0.64 (0.32–1.26) | |
| AA | 7/14 | 1.29 (0.57–2.94) | 5/10 | 1.25 (0.50–3.13) | 2/4 | 1.09 (0.34–3.45) | |
| Log-Add | 180/529 | 1.08 (0.77–1.51) | 123/365 | 1.23 (0.83–1.84) | 57/164 | 0.75 (0.41–1.36) | |
| DICER1 rs3742330 | AA | 150/430 | 1.00 (Ref) | 102/297 | 1.00 (Ref) | 48/133 | 1.00 (Ref) |
| AG | 29/96 | 0.94 (0.59–1.50) | 20/66 | 0.95 (0.55–1.65) | 9/30 | 0.85 (0.40–1.81) | |
| GG | 1/3 | 1.01 (0.31–3.32) | 1/2 | 1.04 (0.31–3.48) | 0/1 | NAC | |
| Log-Add | 180/529 | 0.95 (0.62–1.47) | 123/365 | 0.97 (0.59–1.62) | 57/164 | 0.84 (0.40–1.77) | |
| DDX20 rs197412 | TT | 54/189 | 1.00 (Ref) | 40/140 | 1.00 (Ref) | 14/49 | 1.00 (Ref) |
| TC | 87/254 | 1.27 (0.86–1.88) | 60/169 | 1.39 (0.88–2.19) | 27/85 | 0.94 (0.48–1.86) | |
| CC | 39/86 | 1.67 (1.00–2.80) | 23/56 | 1.48 (0.80–2.72) | 16/30 | 1.68 (0.74–3.81) | |
| Log-Add | 180/529 | 1.34 (1.02–1.75) | 123/365 | 1.31 (0.95–1.80) | 57/164 | 1.39 (0.84–2.29) | |
| GEMIN4 rs2740348 | GG | 123/376 | 1.00 (Ref) | 81/254 | 1.00 (Ref) | 42/122 | 1.00 (Ref) |
| GC | 49/134 | 1.10 (0.74–1.66) | 36/100 | 1.05 (0.65–1.69) | 13/34 | 1.13 (0.56–2.29) | |
| CC | 8/18 | 1.02 (0.47–2.25) | 6/10 | 1.30 (0.53–3.18) | 2/8 | 0.81 (0.26–2.46) | |
| Log-Add | 180/528 | 1.07 (0.77–1.48) | 123/364 | 1.13 (0.77–1.66) | 57/164 | 0.96 (0.53–1.76) | |
| GEMIN4 rs7813 | TT | 67/200 | 1.00 (Ref) | 41/133 | 1.00 (Ref) | 26/67 | 1.00 (Ref) |
| TC | 78/242 | 1.05 (0.72–1.54) | 56/173 | 1.12 (0.70–1.78) | 22/69 | 0.89 (0.48–1.66) | |
| CC | 35/85 | 1.33 (0.81–2.17) | 26/57 | 1.51 (0.84–2.71) | 9/28 | 1.09 (0.49–2.43) | |
| Log-Add | 180/527 | 1.15 (0.89–1.49) | 123/363 | 1.26 (0.92–1.72)c | 57/164 | 1.00 (0.65–1.56) | |
| RAN rs14035 | CC | 85/257 | 1.00 (Ref) | 60/182 | 1.00 (Ref) | 25/75 | 1.00 (Ref) |
| CT | 73/222 | 1.06 (0.72–1.54) | 50/154 | 1.12 (0.72–1.73) | 23/68 | 0.87 (0.45–1.70) | |
| TT | 22/50 | 1.25 (0.72–2.17) | 13/29 | 1.24 (0.64–2.43) | 9/21 | 1.25 (0.55–2.82) | |
| Log-Add | 180/529 | 1.12 (0.85–1.46) | 123/365 | 1.14 (0.83–1.59) | 57/164 | 1.09 (0.69–1.72) | |
| XPO5 rs11077 | AA | 62/175 | 1.00 (Ref) | 44/115 | 1.00 (Ref) | 18/60 | 1.00 (Ref) |
| AC | 82/265 | 0.98 (0.66–1.46) | 55/189 | 0.86 (0.53–1.38) | 27/76 | 1.20 (0.61–2.37) | |
| CC | 34/89 | 1.10 (0.66–1.82) | 23/61 | 1.02 (0.56–1.85) | 11/28 | 1.18 (0.53–2.63) | |
| Log-Add | 178/529 | 1.05 (0.80–1.37) | 122/365 | 0.98 (0.71–1.37) | 56/164 | 1.15 (0.72–1.85) | |
| Candidate genes with SNPs near or within a predicted miRNA binding site | |||||||
| CDK6 rs42031 | AA | 116/335 | 1.00 (Ref) | 80/237 | 1.00 (Ref) | 36/98 | 1.00 (Ref) |
| AT | 55/174 | 0.96 (0.65–1.41) | 37/116 | 1.01 (0.63–1.62) | 18/58 | 0.87 (0.46–1.64) | |
| TT | 8/19 | 1.21 (0.56–2.60) | 5/11 | 1.15 (0.47–2.81) | 3/8 | 1.20 (0.42–3.45) | |
| Log-Add | 179/528 | 1.03 (0.75–1.42) | 122/364 | 1.06 (0.72–1.56) | 57/164 | 1.00 (0.59–1.69) | |
| CXCL12 rs1804429 | TT | 162/498 | 1.00 (Ref) | 112/345 | 1.00 (Ref) | 50/153 | 1.00 (Ref) |
| TG | 18/30 | 1.54 (0.84–2.84) | 11/20 | 1.33 (0.66–2.71) | 7/10 | 1.63 (0.63–4.22) | |
| GG | 0/1 | NAC | 0/0 | NAC | 0/1 | NAC | |
| Log-Add | 180/529 | 1.37 (0.76–2.47) | 123/365 | 1.33 (0.66–2.71) | 57/164 | 1.26 (0.53–2.98) | |
| E2F2 rs2075993 | AA | 43/142 | 1.00 (Ref) | 30/102 | 1.00 (Ref) | 13/40 | 1.00 (Ref) |
| AG | 92/252 | 1.33 (0.85–2.08) | 63/165 | 1.39 (0.84–2.32) | 29/87 | 1.19 (0.57–2.46) | |
| GG | 45/134 | 1.12 (0.67–1.88) | 30/97 | 1.05 (0.59–1.89) | 15/37 | 1.19 (0.51–2.78) | |
| Log-Add | 180/528 | 1.07 (0.81–1.40) | 123/364 | 1.04 (0.76–1.43) | 57/164 | 1.16 (0.68–1.97) | |
| HIF1A rs2057482 | CC | 125/369 | 1.00 (Ref) | 79/266 | 1.00 (Ref) | 46/103 | 1.00 (Ref) |
| CT | 49/147 | 1.09 (0.72–1.65) | 40/92 | 1.67 (1.04–2.70) | 9/55 | 0.42 (0.19–0.94) | |
| TT | 6/12 | 1.17 (0.49–2.77) | 4/6 | 1.64 (0.57–4.67) | 2/6 | 0.69 (0.24–1.96) | |
| Log-Add | 180/528 | 1.11 (0.78–1.57) | 123/364 | 1.73 (1.12–2.67)c | 57/164 | 0.49 (0.25–0.94) | |
| IL15 rs10519613 | CC | 135/433 | 1.00 (Ref) | 89/303 | 1.00 (Ref) | 46/130 | 1.00 (Ref) |
| CA | 42/91 | 1.35 (0.87–2.08) | 32/57 | 1.47 (0.89–2.44) | 10/34 | 0.99 (0.46–2.15) | |
| AA | 2/5 | 1.07 (0.67–3.15) | 2/5 | 1.11 (0.38–3.29) | 0/0 | NAC | |
| Log-Add | 179/529 | 1.29 (0.87–1.91) | 123/365 | 1.38 (0.89–2.15) | 56/164 | 0.99 (0.46–2.15) | |
| IL6R rs4072391 | CC | 117/337 | 1.00 (Ref) | 86/236 | 1.00 (Ref) | 31/101 | 1.00 (Ref) |
| CT | 57/169 | 1.00 (0.69–1.44) | 36/114 | 0.94 (0.60–1.48) | 21/55 | 1.22 (0.65–2.30) | |
| TT | 6/22 | 0.79 (0.36–1.73) | 1/14 | 0.50 (0.18–1.37) | 5/8 | 1.38 (0.51–3.73) | |
| Log-Add | 180/528 | 0.93 (0.68–1.27) | 123/364 | 0.77 (0.52–1.16) | 57/164 | 1.31 (0.79–2.17) | |
| KRAS rs9266 | CC | 52/151 | 1.00 (Ref) | 37/114 | 1.00 (Ref) | 15/37 | 1.00 (Ref) |
| CT | 85/261 | 0.87 (0.57–1.34) | 61/177 | 1.02 (0.62–1.67) | 24/84 | 0.60 (0.29–1.23) | |
| TT | 42/117 | 0.90 (0.55–1.47) | 24/74 | 0.89 (0.50–1.60) | 18/43 | 0.84 (0.39–1.80) | |
| Log-Add | 179/529 | 0.94 (0.72–1.22) | 122/365 | 0.94 (0.69–1.29) | 57/164 | 0.86 (0.54–1.37) | |
| RCHY1 rs2126852 | AA | 102/272 | 1.00 (Ref) | 75/187 | 1.00 (Ref) | 27/85 | 1.00 (Ref) |
| AG | 67/210 | 0.91 (0.63–1.32) | 39/147 | 0.74 (0.47–1.16) | 28/63 | 1.37 (0.73–2.56) | |
| GG | 11/47 | 0.64 (0.33–1.22) | 9/31 | 0.71 (0.34–1.45) | 2/16 | 0.65 (0.23–1.80) | |
| Log-Add | 180/529 | 0.82 (0.61–1.09) | 123/365 | 0.76 (0.54–1.06) | 57/164 | 0.97 (0.58–1.62) | |
| TP53INP1 rs7760 | TT | 134/407 | 1.00 (Ref) | 91/285 | 1.00 (Ref) | 43/122 | 1.00 (Ref) |
| TG | 42/111 | 1.02 (0.67–1.54) | 29/73 | 1.15 (0.71–1.86) | 13/38 | 0.76 (0.37–1.57) | |
| GG | 4/11 | 0.99 (0.38–2.57) | 3/7 | 1.13 (0.40–3.22) | 1/4 | 0.80 (0.24–2.67) | |
| Log-Add | 180/529 | 1.01 (0.71–1.44) | 123/365 | 1.15 (0.76–1.75) | 57/164 | 0.72 (0.37–1.38) | |
| TP53INP1 rs896849 | TT | 121/375 | 1.00 (Ref) | 84/266 | 1.00 (Ref) | 37/109 | 1.00 (Ref) |
| TC | 50/140 | 1.03 (0.69–1.52) | 32/91 | 1.02 (0.64–1.63) | 18/49 | 0.96 (0.50–1.86) | |
| CC | 9/13 | 1.58 (0.70–3.52) | 7/7 | 2.06 (0.82–5.18) | 2/6 | 0.85 (0.28–2.57) | |
| Log-Add | 180/528 | 1.16 (0.83–1.62) | 123/364 | 1.29 (0.87–1.92) | 57/164 | 0.89 (0.50–1.60) | |
a
Cases and controls matched on: cohort (1 or 2), date of infection (continuous); duration of follow-up (continuous); seroconversion status (categorical); race (white or non-white); and CD4+ T-cell count at date of matching (categorical).
b
Adjusted for age at case diagnosis or reference date in controls (continuous); HIV-1 RNA levels before set point (continuous); AIDS diagnosis prior to case diagnosis or reference date in controls (reference=No); history of ART Treatment (reference=No); CD4+ T-cell at reference date (continuous); race (reference=non-Hispanic White); and history of HCV infection (reference=No).
c
Result remained statistically significant in self-reported non-Hispanic White (NHW) subgroup analyses.
NAC: not able to calculate due to limited sample size.
Ca/Co: numbers of cases and controls.
CNS: Central nervous system.
Log-Add: Log-additive model used for effect estimation.