Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Study Design
2.3. Statistics
2.4. Informed Consent
3. Results
3.1. Baseline Characteristics
3.2. Post-Therapy Mixed Cryoglobulinemia in SVR Patients
3.3. Genetic Associations with Baseline HCV RNA
3.4. Genetic Associations with Baseline Mixed Cryoglobulinemia
3.5. Genetic Associations with Post-Therapy Mixed Cryoglobulinemia in SVR Patients
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Borgia, S.M.; Hedskog, C.; Parhy, B.; Hyland, R.H.; Stamm, L.M.; Brainard, D.M.; Subramanian, M.G.; McHutchison, J.G.; Mo, H.; Svarovskaia, E.; et al. Identification of a Novel Hepatitis C Virus Genotype from Punjab, India: Expanding Classification of Hepatitis C Virus into 8 Genotypes. J. Infect. Dis. 2018, 218, 1722–1729. [Google Scholar] [CrossRef] [Green Version]
- Spearman, C.W.; Dusheiko, G.M.; Hellard, M.; Sonderup, M. Hepatitis C. Lancet 2019, 394, 1451–1466. [Google Scholar] [CrossRef]
- Cheng, Y.T.; Cheng, J.S.; Lin, C.H.; Chen, T.H.; Lee, K.C.; Chang, M.L. Rheumatoid factor and immunoglobulin M mark hepatitis C-associated mixed cryoglobulinaemia: An 8-year prospective study. Clin. Microbiol. Infect. 2020, 26, 366–372. [Google Scholar] [CrossRef]
- Chang, M.L. Metabolic alterations and hepatitis C: From bench to bedside. World J. Gastroenterol. 2016, 22, 1461–1476. [Google Scholar] [CrossRef]
- Gragnani, L.; Visentini, M.; Fognani, E.; Urraro, T.; De Santis, A.; Petraccia, L.; Perez, M.; Ceccotti, G.; Colantuono, S.; Mitrevski, M.; et al. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia. Hepatology 2016, 64, 1473–1482. [Google Scholar] [CrossRef] [Green Version]
- Zignego, A.L.; Gragnani, L.; Piluso, A.; Sebastiani, M.; Giuggioli, D.; Fallahi, P.; Antonelli, A.; Ferri, C. Virus-driven autoimmunity and lymphoproliferation: The example of HCV infection.Virus-driven autoimmunity and lymphoproliferation: The example of HCV infection. Expert Rev. Clin. Immunol. 2015, 11, 15–31. [Google Scholar] [CrossRef]
- Praprotnik, S.; Sodin-Semrl, S.; Tomsic, M.; Shoenfeld, Y. The curiously suspicious: Infectious disease may ameliorate an ongoing autoimmune destruction in systemic lupus erythematosus patients. J. Autoimmun. 2008, 30, 37–41. [Google Scholar] [CrossRef]
- Zignego, A.L.; Wojcik, G.L.; Cacoub, P.; Visentini, M.; Casato, M.; Mangia, A.; Latanich, R.; Charles, E.D.; Gragnani, L.; Terrier, B.; et al. Genome-wide association study of hepatitis C virus—and cryoglobulin-related vasculitis. Genes Immun. 2014, 15, 500–505. [Google Scholar] [CrossRef]
- Cusato, J.; Boglione, L.; De Nicolò, A.; Cardellino, C.S.; Carcieri, C.; Cariti, G.; Di Perri, G.; D’Avolio, A. Pharmacogenetic analysis of hepatitis C virus related mixed cryoglobulinemia. Pharmacogenomics 2017, 18, 607–611. [Google Scholar] [CrossRef]
- Piluso, A.; Giannini, C.; Fognani, E.; Gragnani, L.; Caini, P.; Monti, M.; Petrarca, A.; Ranieri, J.; Urraro, T.; Triboli, E.; et al. Value of IL28B genotyping in patients with HCV-related mixed cryoglobulinemia: Results of a large, prospective study. J. Viral. Hepat. 2013, 20, e107–e114. [Google Scholar] [CrossRef]
- Boglione, L.; Cusato, J.; Allegra, S.; Cariti, G.; Di Perri, G.; D’avolio, A. Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment. Arch. Virol. 2015, 160, 2009–2017. [Google Scholar] [CrossRef]
- Taneda, S.; Hudkins, K.L.; Mühlfeld, A.S.; Kowalewska, J.; Pippin, J.W.; Shankland, S.J.; Alpers, C.E. Protease nexin-1, tPA, and PAI-1 are upregulated in cryoglobulinemic membranoproliferative glomerulonephritis. J. Am. Soc. Nephrol. 2008, 19, 243–251. [Google Scholar] [CrossRef] [Green Version]
- Yang, C.H.; Li, H.C.; Ku, T.S.; Wu, P.C.; Yeh, Y.J.; Cheng, J.C.; Lin, T.Y.; Lo, S.Y. Hepatitis C virus down-regulates SERPINE1/PAI-1 expression to facilitate its replication. J. Gen. Virol. 2017, 98, 2274–2286. [Google Scholar] [CrossRef]
- Huang, J.; Sabater-Lleal, M.; Asselbergs, F.W.; Tregouet, D.; Shin, S.Y.; Ding, J.; Baumert, J.; Oudot-Mellakh, T.; Folkersen, L.; Johnson, A.D.; et al. Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation. Blood 2012, 120, 4873–4881. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shimba, S.; Ishii, N.; Ohta, Y.; Ohno, T.; Watabe, Y.; Hayashi, M.; Wada, T.; Aoyagi, T.; Tezuka, M. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc. Natl. Acad. Sci. USA 2005, 102, 12071–12076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ramsey, K.M.; Yoshino, J.; Brace, C.S.; Abrassart, D.; Kobayashi, Y.; Marcheva, B.; Hong, H.K.; Chong, J.L.; Buhr, E.D.; Lee, C.; et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 2009, 324, 651–654. [Google Scholar] [CrossRef] [Green Version]
- Ooi, D.S.; Ong, S.G.; Heng, C.K.; Loke, K.Y.; Lee, Y.S. In-vitro function of upstream visfatin polymorphisms that are associated with adverse cardiometabolic parameters in obese children. BMC Genom. 2016, 17, 974. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stastny, J.; Bienertova-Vasku, J.; Tomandl, J.; Tomandlova, M.; Zlamal, F.; Forejt, M.; Splichal, Z.; Vasku, A. Association of genetic variability in selected regions in visfatin (NAMPT) gene with anthropometric parameters and dietary composition in obese and non-obese Central-European population. Diabetes MetabSyndr. 2013, 7, 166–171. [Google Scholar] [CrossRef] [PubMed]
- Jian, W.X.; Luo, T.H.; Gu, Y.Y.; Zhang, H.L.; Zheng, S.; Dai, M.; Han, J.F.; Zhao, Y.; Li, G.; Luo, M. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population. Diabet. Med. 2006, 23, 967–973. [Google Scholar] [CrossRef] [PubMed]
- Ikeda, Y.; Tsuchiya, H.; Hama, S.; Kajimoto, K.; Kogure, K. Resistin regulates the expression of plasminogen activator inhibitor-1 in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 2014, 448, 129–133. [Google Scholar] [CrossRef] [PubMed]
- Chang, M.L.; Liang, K.H.; Ku, C.L.; Lo, C.C.; Cheng, Y.T.; Hsu, C.M.; Yeh, C.T.; Chiu, C.T. Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms. Sci. Rep. 2016, 6, 30799. [Google Scholar] [CrossRef] [Green Version]
- Hivert, M.F.; Manning, A.K.; McAteer, J.B.; Dupuis, J.; Fox, C.S.; Cupples, L.A.; Meigs, J.B.; Florez, J.C. Association of variants in RETN with plasma resistin levels and diabetes-related traits in the Framingham Offspring Study. Diabetes 2009, 58, 750–756. [Google Scholar] [CrossRef] [Green Version]
- Hu, J.H.; Chen, M.Y.; Yeh, C.T.; Lin, H.S.; Lin, M.S.; Huang, T.J.; Chang, M.L. Sexual Dimorphic Metabolic Alterations in Hepatitis C Virus-infected Patients: A Community-Based Study in a Hepatitis B/Hepatitis C Virus Hyperendemic Area. Med. Baltim. 2016, 95, e3546. [Google Scholar] [CrossRef]
- Lee, K.C.; Cheng, Y.T.; Lin, C.Y.; Kuo, C.J.; Chien, R.N.; Yeh, C.T.; Chang, M.L. Impact of mixed cryoglobulinemia on patients with spontaneous hepatitis C virus clearance: A 13-year prospective cohort study. Eur. J. Clin. Investig. 2020, 50, e13189. [Google Scholar] [CrossRef]
- Gragnani, L.; Fognani, E.; De Re, V.; Libra, M.; Garozzo, A.; Caini, P.; Cerretelli, G.; Giovannelli, A.; Lorini, S.; Monti, M.; et al. Notch4 and mhc class II polymorphisms are associated with hcv-related benign and malignant lymphoproliferative diseases. Oncotarget 2017, 8, 71528–71535. [Google Scholar] [CrossRef] [Green Version]
- Zhang, K.; Zhou, B.; Zhang, P.; Zhang, Z.; Chen, P.; Pu, Y.; Song, Y.; Zhang, L. Genetic variants in NAMPT predict bladder cancer risk and prognosis in individuals from southwest Chinese Han group. Tumour Biol. 2014, 35, 4031–4040. [Google Scholar] [CrossRef]
- Motyckova, G.; Murali, M. Laboratory testing for cryoglobulins. Am. J. Hematol. 2011, 86, 500–502. [Google Scholar] [CrossRef]
- Hsieh, A.R.; Chang, S.W.; Chen, P.L.; Chu, C.C.; Hsiao, C.L.; Yang, W.S.; Chang, C.C.; Wu, J.Y.; Chen, Y.T.; Chang, T.C.; et al. Predicting HLA genotypes using unphased and flanking single-nucleotide polymorphisms in Han Chinese population. BMC Genom. 2014, 15, 81. [Google Scholar] [CrossRef] [Green Version]
- Yang, H.C.; Lin, C.H.; Hsu, C.L.; Hung, S.I.; Wu, J.Y.; Pan, W.H.; Chen, Y.T.; Fann, C.S. A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians. J. Biomed. Sci. 2006, 13, 489–498. [Google Scholar] [CrossRef]
- Benjamini, Y.; Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Methodol. 1995, 57, 289–300. [Google Scholar] [CrossRef]
- Fairweather, D.; Rose, N.R. Women and autoimmune diseases. Emerg. Infect. Dis. 2004, 10, 2005–2011. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klein, S.L. Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases. Bioessays 2012, 34, 1050–1059. [Google Scholar] [CrossRef] [Green Version]
- Grebely, J.; Page, K.; Sacks-Davis, R.; van der Loeff, M.S.; Rice, T.M.; Bruneau, J.; Morris, M.D.; Hajarizadeh, B.; Amin, J.; Cox, A.L.; et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology 2014, 59, 109–120. [Google Scholar] [CrossRef] [Green Version]
- Ge, D.; Fellay, J.; Thompson, A.J.; Simon, J.S.; Shianna, K.V.; Urban, T.J.; Heinzen, E.L.; Qiu, P.; Bertelsen, A.H.; Muir, A.J.; et al. Genetic variationin IL28B predicts hepatitis Ctreatment-induced viral clearance. Nature 2009, 461, 399–401. [Google Scholar] [CrossRef]
- Thio, C.L.; Thomas, D.L.; Goedert, J.J.; Vlahov, D.; Nelson, K.E.; Hilgartner, M.W.; O’Brien, S.J.; Karacki, P.; Marti, D.; Astemborski, J.; et al. Racial differences in HLA class II associations with hepatitis C virus outcomes. J. Infect. Dis. 2001, 184, 16–21. [Google Scholar] [CrossRef]
- Honegger, J.R.; Tedesco, D.; Kohout, J.A.; Prasad, M.R.; Price, A.A.; Lindquist, T.; Ohmer, S.; Moore-Clingenpeel, M.; Grakoui, A.; Walker, C.M. Influence of IFNL3 and HLA-DPB1 genotype on postpartum control of hepatitis C virus replication and T-cell recovery. Proc. Natl. Acad. Sci. USA 2016, 113, 10684–10689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harris, R.A.; Sugimoto, K.; Kaplan, D.E.; Ikeda, F.; Kamoun, M.; Chang, K.M. Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans. Hepatology 2008, 48, 70–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ding, Y.; Li, X. Resistin Promotes Thrombosis in Rats with Deep Vein Thrombosis via Up-Regulating MMP-2, MMP-9, and PAI-1. Clin. Lab. 2019, 65. [Google Scholar] [CrossRef] [PubMed]
- Chang, M.L.; Lin, Y.S.; Pao, L.H.; Huang, H.C.; Chiu, C.T. Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance. Sci. Rep. 2017, 7, 42503. [Google Scholar] [CrossRef] [Green Version]
GENE | Gentype | Total (n = 1043) | CHC (n = 934) | Spontaneous HCV Clearance (n = 109) | p Values (CHC vs. SHC) | |
---|---|---|---|---|---|---|
Female, n (%) | 520 (49.9) | 449 (48.1) | 71 (65.1) | 0.001 | ||
Age (years old) | 57.0 ± 12.95 | 57.1 ± 12.8 | 54.3 ± 13.9 | 0.031 | ||
Mixed cryoglobulinemia, n (%) | 589 (56.5) | 550 (58.9) | 39 (35.8) | <0.001 | ||
Log HCV RNA (logIU/mL) | 6.04 ± 1.01 | 6.04 ± 1.00 | NA | |||
HCV genotype | ||||||
Genotype 1, n (%) | 550 (52.7) | 500 (53.5) | NA | |||
Genotype 2, n (%) | 300 (28.8) | 300 (32.1) | NA | |||
Others, n (%) | 134 (12.8) | 134 (14.3) | NA | |||
ALT(U/L) | 88.3 ± 99.42 | 93.6 ± 102.0 | 42.2 ± 54.3 | <0.001 | ||
rs12979860, n (%) | IFNL3 | CC | 891 (85.4) | 791 (84.7) | 100 (91.7) | 0.01 |
rs6486122, n (%) | ARNTL | TT | 224 (21.4) | 207 (22.2) | 17 (15.6) | 0.09 |
rs1045642, n (%) | ABCB1 | GG | 422 (40.5) | 377 (40.4) | 45 (41.3) | 0.399 |
rs9461776, n (%) | HLA-II | AA | 871 (83.3) | 791 (84.7) | 80 (73.4) | 0.003 |
rs2071286, n (%) | NOTCH4 | CC | 774 (74.2) | 701 (75.1) | 73 (67) | 0.083 |
rs6976053, n (%) | SERPINE1 | CC | 292 (27.9) | 289 (30.9) | 3 (2.8) | <0.001 |
rs11128603, n (%) | PPARG | TT | 943 (90.2) | 850 (91.0) | 93 (85.3) | 0.44 |
rs61330082, n (%) | NAMPT | TT | 178 (17) | 166 (17.8) | 12 (11) | 0.46 |
rs10953502, n (%) | NAMPT | TT | 599 (57.3) | 554 (59.3) | 45 (41.3) | 0.132 |
rs2302559, n (%) | NAMPT | CC | 624 (59.7) | 576 (61.7) | 48 (44) | 0.14 |
rs2058539, n (%) | NAMPT | AA | 608 (58.2) | 562 (60.2) | 46 (42) | 0.297 |
rs1423096, n (%) | RETN | CC | 670 (64.2) | 595 (63.7) | 75 (69.2) | 0.92 |
rs1477341, n (%) | RETN | AA | 343 (32.9) | 308 (33.0) | 35 (32.1) | 0.332 |
Genotype | Mixed Cryoglobulinemia (+) (n = 589) | MixecdCryoglobulinemia (−) (n = 454) | p Values | |
---|---|---|---|---|
Female, n (%) | 326 (55.3) | 194 (42.7) | <0.01 | |
Age (years old) | 58.04 ± 12.62 | 55.21 ± 13.21 | <0.01 | |
HCV RNA positivity | 550 (93.4) | 384 (84.6) | <0.001 | |
Log HCV RNA (logIU/mL) | 5.91 ± 1.04 | 6.23 ± 0.92 | <0.001 | |
ALT(U/L) | 93.87 ± 98.71 | 81.08 ± 99.98 | 0.04 | |
rs12979860, n (%) | CC | 515 (87.4) | 378 (82.8) | 0.026 |
rs6486122, n (%) | TT | 138 (23.4) | 86 (18.9) | 0.033 |
rs1045642, n (%) | GG | 239 (40.6) | 183 (40.3) | 0.745 |
rs9461776, n (%) | AA | 488 (82.9) | 383 (84.4) | 0.449 |
rs2071286, n (%) | CC | 440 (74.7) | 334 (73.6) | 0.552 |
rs6976053, n (%) | CC | 175 (29.7) | 117 (25.7) | 0.384 |
rs11128603, n (%) | TT | 532 (90.3) | 411 (90.5) | 0.692 |
rs61330082, n (%) | TT | 96 (16.3) | 82 (18.1) | 0.867 |
rs10953502, n (%) | TT | 334 (56.7) | 265 (58.4) | 0.108 |
rs2302559, n (%) | CC | 358 (60.8) | 266 (58.6) | 0.745 |
rs2058539, n (%) | AA | 342 (58.1) | 266 (58.6) | 0.205 |
rs1423096, n (%) | CC | 386 (65.5) | 283 (62.3) | 0.381 |
rs1477341, n (%) | AA | 185 (31.4) | 163 (35.9) | 0.465 |
Reference Allele/Risk Allele | Univariate Analyses | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
OR | 95% CI OR | p Values | OR | 95% CI OR | p Values | ||
Baseline MC (0,1) | 2.618 | 1.726–3.969 | <0.001 | 2.617 | 1.679–4.079 | <0.001 | |
rs12979860- | C/T | 3.72 | 1.397–9.905 | 0.009 | 3.755 | 1.378–10.235 | 0.01 |
rs1045642- | G/A | 1.164 | 0.856–1.582 | 0.332 | |||
rs9461776 | G/A | 1.751 | 1.125–2.276 | 0.013 | 1.783 | 1.106–2.876 | 0.018 |
rs2071286 | C/T | 0.656 | 0.441–0.974 | 0.037 | 0.711 | 0.468–1.08 | 0.11 |
rs6976053 | T/C | 2.871 | 2.045–4.131 | <0.001 | 2.737 | 1.93–3.881 | <0.001 |
rs6486122 | C/T | 0.942 | 0.725–1.224 | 0.657 | |||
rs11128603- | G/A | 0.744 | 0.29–1.911 | 0.539 | |||
rs61330082- | C/T | 0.9 | 0.603–1.343 | 0.605 | |||
rs2302559- | C/T | 1.867 | 0.859–4.056 | 0.115 | |||
rs10953502- | C/T | 1.243 | 0.591–2.616 | 0.567 | |||
rs2058539- | C/T | 0.519 | 0.232–1.162 | 0.111 | |||
rs1423096- | C/T | 1.182 | 0.48–2.906 | 0.716 | |||
rs1477341- | A/T | 0.728 | 0.191–2.772 | 0.642 |
Reference Allele/Risk Allele | Univariate Analyses | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
OR | 95% CI OR | p Values | OR | 95% CI OR | p Values | ||
HCV RNA positivity | 2.618 | 1.726–3.969 | <0.001 | 2.556 | 1.673–3.915 | <0.001 | |
rs12979860 | T/C | 1.142 | 1.01–1.974 | 0.044 | 1.531 | 1.087–2.056 | 0.015 |
rs1045642 | G/A | 1.016 | 0.835–1.236 | 0.877 | |||
rs9461776 | G/A | 0.917 | 0.648–1.298 | 0.624 | |||
rs2071286 | C/T | 0.894 | 0.672–1.188 | 0.44 | |||
rs6976053 | T/C | 0.907 | 0.776–1.062 | 0.226 | |||
rs6486122 | C/T | 1.19 | 1.002–1.414 | 0.048 | 1.191 | 1.000–1.419 | 0.049 |
rs11128603 | G/A | 0.943 | 0.547–1.624 | 0.832 | |||
rs61330082 | C/T | 0.937 | 0.751–1.168 | 0.56 | |||
rs2302559 | C/T | 0.901 | 0.653–1.244 | 0.527 | |||
rs10953502 | C/T | 1.293 | 0.89–1.877 | 0.177 | |||
rs2058539 | C/T | 0.796 | 0.56–1.113 | 0.205 | |||
rs1423096 | C/T | 0.854 | 0.656–1.112 | 0.241 | |||
rs1477341 | A/T | 0.961 | 0.73–1.264 | 0.774 |
Reference Allele/Risk Allele | Univariate Analyses | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
OR | 95% CI OR | p Values | OR | 95% CI OR | p Values | ||
Pre-therapy mixed cryoglobulinemia | 3.143 | 2.16–4.575 | <0.001 | 3.113 | 1.895–5.116 | <0.001 | |
rs12979860 | T/C | 1.283 | 0.763–2.159 | 0.348 | |||
rs1045642 | G/A | 1.031 | 0.774–1.372 | 0.835 | |||
rs9461776 | G/A | 1.068 | 0.649–1.757 | 0.797 | |||
rs2071286 | C/T | 1.035 | 0.678–1.58 | 0.874 | |||
rs6976053 | C/T | 0.933 | 0.746–1.166 | 0.541 | |||
rs6486122 | C/T | 1.024 | 0.802–1.308 | 0.85 | |||
rs11128603 | G/A | 1.414 | 0.585–3.42 | 0.442 | |||
rs61330082 | C/T | 0.857 | 0.64–1.147 | 0.299 | |||
rs2302559 | C/T | 1.142 | 0.734–1.776 | 0.557 | |||
rs10953502 | C/T | 1.013 | 0.588–1.743 | 0.964 | |||
rs2058539 | C/T | 0.989 | 0.601–1.627 | 0.965 | |||
rs1423096 | C/T | 0.652 | 0.45–0.944 | 0.023 | 0.677 | 0.46–0.995 | 0.047 |
rs1477341 | A/T | 0.794 | 0.589–1.072 | 0.132 |
Reference Allele/Risk Allele | Univariate Analyses | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95% CI HR | p Values | HR | 95% CI HR | p Values | ||
24-week post-therapy mixed cryoglobulinemia (0,1) | 3.145 | 1.997–4.952 | <0.001 | 2.829 | 1.779–4.497 | <0.001 | |
rs12979860 | T/C | 1.76 | 0.911–3.403 | 0.093 | 1.888 | 0.867–4.114 | 0.11 |
rs1045642 | G/A | 0.906 | 0.669–1.229 | 0.526 | |||
rs9461776 | G/A | 2.121 | 0.985–4.566 | 0.055 | 1.982 | 0.927–4.235 | 0.078 |
rs2071286 | C/T | 0.971 | 0.605–1.558 | 0.903 | |||
rs6976053 | C/T | 1.313 | 1.023–1.694 | 0.032 | 1.351 | 1.046–1.746 | 0.021 |
rs6486122 | C/T | 0.861 | 0.661–1.122 | 0.268 | |||
rs11128603 | G/A | 0.719 | 0.332–1.56 | 0.404 | |||
rs61330082 | C/T | 1.144 | 0.839–1.56 | 0.396 | |||
rs2302559 | C/T | 0.927 | 0.559–1.538 | 0.769 | |||
rs10953502 | C/T | 0.825 | 0.412–1.653 | 0.588 | |||
rs2058539 | C/T | 1.194 | 0.61–2.34 | 0.605 | |||
rs1423096 | C/T | 0.798 | 0.538–1.183 | 0.261 | |||
rs1477341 | A/T | 1.141 | 0.787–1.654 | 0.487 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chang, M.-L.; Chang, S.-W.; Chen, S.-C.; Chien, R.-N.; Hsu, C.-L.; Chang, M.-Y.; Fann, C.S.J. Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals. Viruses 2021, 13, 464. https://doi.org/10.3390/v13030464
Chang M-L, Chang S-W, Chen S-C, Chien R-N, Hsu C-L, Chang M-Y, Fann CSJ. Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals. Viruses. 2021; 13(3):464. https://doi.org/10.3390/v13030464
Chicago/Turabian StyleChang, Ming-Ling, Su-Wei Chang, Shiang-Chi Chen, Rong-Nan Chien, Chia-Lin Hsu, Ming-Yu Chang, and Cathy S. J. Fann. 2021. "Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals" Viruses 13, no. 3: 464. https://doi.org/10.3390/v13030464
APA StyleChang, M. -L., Chang, S. -W., Chen, S. -C., Chien, R. -N., Hsu, C. -L., Chang, M. -Y., & Fann, C. S. J. (2021). Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals. Viruses, 13(3), 464. https://doi.org/10.3390/v13030464