Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Genotyping
2.3. Determination of Cytokine Levels
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics and IL-1β Genotype Distribution
3.2. Association of the IL-1β SNPs with Liver Cirrhosis
3.3. Association of the IL-1β SNPs with HCC
3.4. Haplotype Analysis of IL-1β rs1143627 and rs16944
3.5. Effect of rs1143627 and rs16944 on IL-1β Serum Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Baseline Parameter | HBeAg-Negative CHB (n = 255) | HBeAg-Positive CHB (n = 99) | IC State (n = 278) | HBeAg-Negative vs. HBeAg-Positive CHB ‡ | HBeAg-Negative CHB vs. IC State ‡ | HBeAg-Positive CHB vs. IC State ‡ |
---|---|---|---|---|---|---|
Age (years) † | 56.7 ± 13.5 | 53.9 ± 14.3 | 51.4 ± 13.5 | 0.093 | 2.18 × 10−5 | 0.188 |
Male | 174 (68.2%) | 76 (76.8%) | 144 (51.8%) | 0.121 | 0.0001 | 1.61 × 10−5 |
HBV DNA (log10 IU/mL) † | 3.6 ± 2.5 | 6.1 ± 2.2 | 2.0 ± 1.2 | 1.82 × 10−16 | 6.54 × 10−16 | 3.06 × 10−34 |
ALT (IU/mL) † | 87.5 ± 204.2 | 79.2 ± 104.1 | 31.6 ± 25.0 | 0.044 | 1.52 × 10−15 | 3.67 × 10−14 |
Diabetes | 23 (9.0%) | 9 (9.1%) | 22 (7.9%) | 1.000 | 0.755 | 0.676 |
FIB-4 score † | 2.98 ± 6.41 | 1.99 ± 2.86 | 1.18 ± 0.80 | 0.054 | 4.20 × 10−5 | 0.329 |
Liver cirrhosis | 70 (27.5%) | 24 (24.2%) | 11 (4.0%) | 0.566 | 0.003 | 0.003 |
HCC | 41 (16.1%) | 12 (12.1%) | 11 (4.0%) | 0.733 | 0.001 | 0.031 |
AFP (n = 115) | 286.4 ± 1421.4 | 4.8 ± 4.7 | 4.5 ± 8.2 | 0.705 | 0.043 | 0.542 |
NUC treatment | 214 (83.9%) | 94 (95.0%) | 52 (18.7%) | 0.005 | 5.57 × 10−55 | 8.22 × 10−44 |
Descent Northern/Central or Eastern Europe | 174 (68.2%) | 65 (65.7%) | 163 (58.6%) | |||
Middle East | 4 (1.6%) | 2 (2.0%) | 13 (4.7%) | 0.776 | 0.020 | 0.365 |
Mediterranean | 77 (30.2%) | 32 (32.3%) | 102 (36.7%) |
IL1-β | LC (n = 105) | No LC (n = 527) | Unadjusted OR [95% CI] | p-Value | Adjusted OR [95% CI] | p-Value | |
---|---|---|---|---|---|---|---|
rs1143623 | CC | 56 (53.3%) | 268 (50.9%) | REF | |||
CG | 40 (38.1%) | 221 (41.9%) | 0.87 [0.56–1.35] | 0.252 | |||
GG | 9 (8.6%) | 38 (7.2%) | 1.13 [0.52–2.48] | 0.753 | |||
GG/CG vs. CC | 0.91 [0.60–1.38] | 0.643 | |||||
GG vs. CG/CC | 1.21 [0.57–2.57] | 0.628 | |||||
rs1143627 | CC | 16 (15.2%) | 81 (15.4%) | REF | |||
CT | 47 (44.8%) | 269 (51.0%) | 0.89 [0.48–1.64] | 0.570 | |||
TT | 42 (40.0%) | 177 (33.6%) | 1.20 [0.64–2.26] | 0.698 | |||
TT/CT vs. CC | 1.01 [0.56–1.81] | 0.973 | |||||
TT vs. CT/CC | 1.32 [0.86–2.03] | 0.208 | |||||
rs16944 | TT | 14 (13.4%) | 71 (13.5%) | REF | |||
CT | 51 (54.0%) | 290 (55.0%) | 0.88 [0.46–1.68] | 0.996 | |||
CC | 40 (32.6%) | 166 (31.5%) | 1.19 [0.61–2.33] | 0.610 | |||
CC/CT vs. TT | 1.00 [0.54–1.84] | 0.989 | |||||
CC vs. CT/TT | 1.32 [0.85–2.03] | 0.217 | |||||
Male sex | 95 (90.5%) | 299 (56.7%) | 7.24 [3.69–14.21] | 8.50 × 10−9 | 5.68 [2.49–12.98] | 3.78 × 10−5 | |
Age (years) † | 65.6 ± 10.2 | 51.6 ± 13.2 | 1.10 [1.07–1.12] | 3.29 × 10−17 | 1.09 [1.06–1.12] | 1.43 × 10−9 | |
HBV DNA (log10 IU/mL) † | 3.59 ± 2.95 | 3.33 ± 2.26 | 1.05 [0.95–1.15] | 0.339 | |||
ALT (IU/mL) † | 119.8 ± 289.8 | 50.0 ± 77.4 | 1.00 [1.00–1.01] | 0.0004 | 1.00 [1.00–1.00] | 0.377 | |
Diabetes | 19 (18.1%) | 35 (6.6%) | 3.11 [1.70–5.68] | 0.0002 | 1.90 [0.83–4.34] | 0.127 | |
FIB-4 score | 5.20 ± 5.17 | 1.46 ± 4.03 | 1.37 [1.23–1.52] | 1.17 × 10−8 | 1.08 [1.00–1.16] | 0.040 | |
IC | 11 (10.4%) | 267 (50.7%) | REF | ||||
HBeAg-positive CHB | 24 (22.9%) | 75 (14.2%) | 7.77 [3.64–16.58] | 1.17 × 10−7 | 6.56 [1.68–25.57] | 0.007 | |
HBeAg-negative CHB | 70 (66.7%) | 185 (35.1%) | 9.18 [4.73–17.82] | 8.46 × 10−11 | 8.56 [2.57–28.55] | 0.0005 | |
NUC treatment | 82 (78.1%) | 278 (52.8%) | 3.19 [1.95–5.23] | 3.93 × 10−6 | 0.99 [0.31–3.11] | 0.980 | |
Descent Northern/Central or Eastern Europe | 90 (85.7%) | 312 (59.2%) | 4.39 [2.39–8.07] | 1.84 × 10−6 | 1.95 [0.92–4.14] | 0.083 | |
Middle East | 2 (1.9%) | 17 (3.2%) | 1.79 [0.37–8.60] | 0.466 | 1.44 [0.15–14.37] | 0.755 | |
Mediterranean | 13 (12.4%) | 198 (37.6%) | REF |
IL1-β | HCC (n = 64) | No HCC (n = 568) | Unadjusted OR [95% CI] | p-Value | Adjusted OR [95% CI] | p-Value | |
---|---|---|---|---|---|---|---|
rs1143623 | CC | 34 (53.1%) | 290 (51.1%) | REF | |||
CG | 26 (40.6%) | 235 (41.4%) | 0.94 [0.55–1.62] | 0.833 | |||
GG | 4 (6.3%) | 43 (7.6%) | 0.79 [0.27–2.35] | 0.676 | |||
GG/CG vs. CC | 0.92 [0.55–1.55] | 0.754 | |||||
GG vs. CG/CC | 0.81 [0.49–2.02] | 0.703 | |||||
rs1143627 | CC | 9 (14.1%) | 88 (15.5%) | REF | REF | ||
CT | 24 (37.5%) | 292 (51.4%) | 0.81 [0.36–1.79] | 0.593 | |||
TT | 31 (48.4%) | 188 (33.1%) | 1.61 [0.74–3.53] | 0.232 | |||
TT/CT vs. CC | 1.12 [0.53–2.35] | 0.978 | |||||
TT vs. CT/CC | 1.90 [1.13–3.20] | 0.016 | 0.52 [0.12–2.19] | 0.370 | |||
rs16944 | TT | 7 (10.9%) | 77 (13.6%) | REF | REF | ||
CT | 27 (42.2%) | 316 (55.6%) | 0.84 [0.35–2.01] | 0.833 | |||
CC | 30 (46.9%) | 175 (30.8%) | 2.07 [0.88–4.90] | 0.096 | |||
CC/CT vs. TT | 1.28 [0.56–2.90] | 0.559 | |||||
CC vs. CT/TT | 2.39 [1.42–4.03] | 0.001 | 6.44 [1.50–27.59] | 0.012 | |||
Male sex | 58 (90.6%) | 336 (59.2%) | 6.68 [2.83–15.73] | 1.42 × 10−5 | 5.86 [1.47–23.31] | 0.012 | |
Age (years) † | 64.4 ± 11.2 | 52.7 ± 13.5 | 1.07 [1.05–1.09] | 7.72 × 10−9 | 1.06 [1.02–1.10] | 0.005 | |
HBV DNA (log10 IU/mL) † | 3.57 ± 2.61 | 3.35 ± 2.36 | 1.04 [0.92–1.17] | 0.532 | |||
ALT (IU/mL) † | 94.0 ± 141.4 | 58.8 ± 140.8 | 1.00 [1.00–1.00] | 0.188 | |||
Diabetes | 9 (14.1%) | 45 (7.9%) | 1.90 [0.88–4.10] | 0.101 | |||
IC | 11 (17.2%) | 267 (47.0%) | REF | ||||
HBeAg-positive CHB | 12 (18.7%) | 87 (15.3%) | 3.34 [1.43–7.86] | 0.006 | 1.65 [0.37–7.29] | 0.508 | |
HBeAg-negative CHB | 41 (63.1%) | 214 (37.7%) | 4.65 [2.33–9.27] | 1.25 × 10−5 | 2.50 [0.72–8.73] | 0.150 | |
FIB-4 score | 4.11 ± 3.86 | 1.90 ± 4.47 | 1.06 [1.01–1.12] | 0.029 | 0.93 [0.84–1.04] | 0.187 | |
Presence of LC | 49 (76.6%) | 56 (9.9%) | 29.87 [15.74–56.69] | 2.76 × 10−25 | 17.20 [6.27–47.19] | 3.31 × 10−8 | |
NUC treatment | 40 (62.5%) | 320 (56.3%) | 1.29 [0.76–2.20] | 0.346 | |||
Descent Northern/Central or Eastern Europe | 59 (92.2%) | 343 (60.4%) | 8.90 [3.19–24.87] | 3.30 × 10−5 | 2.63 [0.76–9.12] | 0.127 | |
Middle East | 1 (1.6%) | 18 (3.2%) | 2.88 [0.31–27.10] | 0.356 | 3.20 [0.23–44.33] | 0.386 | |
Mediterranean | 4 (6.3%) | 207 (36.4%) |
IL1-β | HCC (n = 52) | No HCC (n = 183) | Unadjusted OR [95% CI] | p-Value | Adjusted OR [95% CI] | p-Value | |
---|---|---|---|---|---|---|---|
rs1143623 | CC | 28 (53.8%) | 97 (53.0%) | REF | |||
CG | 21 (40.4%) | 71 (38.8%) | 1.03 [0.54–1.95] | 0.941 | |||
GG | 3 (5.8%) | 15 (8.2%) | 0.69 [0.19–2.57] | 0.583 | |||
GG/CG vs. CC | 0.97 [0.52–1.79] | 0.915 | |||||
GG vs. CG/CC | 0.69 [0.19–2.47] | 0.563 | |||||
rs1143627 | CC | 6 (11.5%) | 23 (12.6%) | REF | |||
CT | 21 (40.4%) | 92 (50.3%) | 0.88 [0.32–2.42] | 0.797 | |||
TT | 25 (48.1%) | 68 (37.2%) | 1.41 [0.52–3.86] | 0.505 | |||
TT/CT vs. CC | 1.40 [0.42–2.87] | 0.842 | |||||
TT vs. CT/CC | 1.57 [0.84–2.91] | 0.157 | |||||
rs16944 | TT | 4 (7.7%) | 21 (11.5%) | REF | REF | ||
CT | 21 (40.4%) | 99 (54.1%) | 1.11 [0.35–3.58] | 0.857 | |||
CC | 27 (51.9%) | 63 (34.4%) | 2.25 [0.71–7.18] | 0.171 | |||
CC/CT vs. TT | 1.95 [0.51–4.75] | 0.438 | |||||
CC vs. CT/TT | 2.06 [1.10–3.84] | 0.023 | 4.16 [1.79–9.71] | 0.001 | |||
Male sex | 41 (91.1%) | 106 (57.9%) | 8.72 [3.02–25.20] | 6.38 × 10−5 | 5.94 [1.77–19.89] | 0.004 | |
Age (years) † | 68.3 ± 8.1 | 68.3 ± 6.7 | 1.00 [0.95–1.04] | 0.899 | |||
HBV DNA (log10 IU/mL) † | 3.55 ± 2.50 | 3.30 ± 2.62 | 1.01 [0.89–1.15] | 0.856 | |||
ALT (IU/mL) † | 94.0 ± 141.4 | 58.8 ± 140.8 | 1.00 [1.00–1.00] | 0.206 | |||
Diabetes | 8 (15.4%) | 31 (16.9%) | 0.52 [0.19–1.42] | 0.202 | |||
IC state | 10 (19.2%) | 74 (40.4%) | REF | ||||
HBeAg-positive CHB | 9 (17.3%) | 26 (14.2%) | 2.56 [0.94–7.00] | 0.067 | 0.74 [0.20–2.72] | 0.652 | |
HBeAg-negative CHB | 33 (63.5%) | 83 (45.4%) | 2.94 [1.36–6.38] | 0.006 | 0.68 [0.24–1.94] | 0.474 | |
FIB-4 score | 4.12 ± 2.43 | 3.30 ± 6.97 | 1.02 [0.97–1.06] | 0.487 | |||
Presence of LC | 42 (80.8%) | 37 (20.2%) | 16.57 [7.61–36.09] | 1.54 × 10−12 | 16.90 [6.49–44.00] | 6.99 × 10−9 | |
NUC treatment | 33 (63.5%) | 118 (64.5%) | 0.96 [0.50–1.82] | 0.892 | |||
Descent Northern/Central or Eastern Europe | 47 (90.4%) | 151 (82.5%) | 2.33 [0.78–6.97] | 0.129 | |||
Middle East | 7 (7.7%) | 30 (16.4%) | 3.75 [0.27–51.37] | 0.322 | |||
Mediterranean | 1 (1.9%) | 2 (1.1%) | REF |
rs1143627/rs16944 Haplotypes | Frequency | OR [95% CI] | p-Value | ||
---|---|---|---|---|---|
Overall | No HCC | HCC | |||
TC | 0.565 | 0.553 | 0.672 | 1.55 [1.04–2.32] | 0.031 |
CT | 0.371 | 0.379 | 0.297 | REF | REF |
CC | 0.033 | 0.035 | 0.031 | 1.13 [0.39–3.34] | 0.819 |
TT | 0.031 | 0.033 | 0 | 0 | 0.998 |
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Fischer, J.; Long, S.; Koukoulioti, E.; Müller, T.; Fueloep, B.; Heyne, R.; Eslam, M.; George, J.; Finkelmeier, F.; Waidmann, O.; et al. Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B. Pathogens 2023, 12, 54. https://doi.org/10.3390/pathogens12010054
Fischer J, Long S, Koukoulioti E, Müller T, Fueloep B, Heyne R, Eslam M, George J, Finkelmeier F, Waidmann O, et al. Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B. Pathogens. 2023; 12(1):54. https://doi.org/10.3390/pathogens12010054
Chicago/Turabian StyleFischer, Janett, Shuang Long, Eleni Koukoulioti, Tobias Müller, Balazs Fueloep, Renate Heyne, Mohammed Eslam, Jacob George, Fabian Finkelmeier, Oliver Waidmann, and et al. 2023. "Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B" Pathogens 12, no. 1: 54. https://doi.org/10.3390/pathogens12010054
APA StyleFischer, J., Long, S., Koukoulioti, E., Müller, T., Fueloep, B., Heyne, R., Eslam, M., George, J., Finkelmeier, F., Waidmann, O., Berg, T., & van Bömmel, F. (2023). Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B. Pathogens, 12(1), 54. https://doi.org/10.3390/pathogens12010054