Table 2.
Host genetic factors associated with chronic HBV infection.
| Category | Gene ontology | Gene | Genetic determinants (SNP/Hap/CNVs) | Main reference |
|---|---|---|---|---|
| I | HLA | HLA-B | *07, *58 | Seshasubramanian et al., 2018 |
| HLA-DPA1 | rs3077 | Kamatani et al., 2009; Mbarek et al., 2011; Yan et al., 2012b; Jiang et al., 2015 | ||
| HLA-DPB1 | rs2281388, rs9277535, rs9277542 | Kamatani et al., 2009; Mbarek et al., 2011; Nishida et al., 2012; Yan et al., 2012b; Zhang et al., 2013b; Jiang et al., 2015; Trinks et al., 2017 | ||
| HLA-DQ | rs9275319, rs9275572 | Al-Qahtani et al., 2014; Zhang et al., 2014b; Kim et al., 2015; Xu et al., 2018 | ||
| HLA-DQB1 | *0201, *0301, *0303, *0502, *0604, rs2856718 | Mbarek et al., 2011; Jiang et al., 2015; Huang et al., 2016; Xu et al., 2017b; Xu et al., 2018 | ||
| HLA-DQB2 | rs7453920 | Hu et al., 2013; Jiang et al., 2015; Xu et al., 2017b; Xu et al., 2018 | ||
| HLA-DRB1 | *13 | Zhu et al., 2016b | ||
| Cytokines | IL-10 | −592 | Cheong et al., 2006; Chen et al., 2010 | |
| IL-18 | −137 | Karra et al., 2015 | ||
| IFN-γ | +874 | Sun et al., 2015 | ||
| TNF-α | −238, −308, −857, −863 | Kim et al., 2003; Cheong et al., 2006; Shi et al., 2012; Zheng et al., 2012 | ||
| Chemokines | CCR5 | Δ32 | Suneetha et al., 2006 | |
| TLRs | TLR-3 | rs3775291 | Geng et al., 2016 | |
| MicroRNAs | MiR-106b-25 | rs999885 | Liu et al., 2012b; Zhou et al., 2015 | |
| miR-122 | rs3783553 | Zhou et al., 2015 | ||
| miR-196a-2 | rs11614913 | Zhou et al., 2015; Al-Qahtani et al., 2017 | ||
| miR-let-7c | rs6147150 | Zhou et al., 2015 | ||
| Others | CTLA-4 | rs231775, rs5742909 | Schott et al., 2007; Huang et al., 2013; Xu et al., 2013 | |
| NTCP | rs2296651 | Hu et al., 2016; Wang et al., 2017a; Nfor et al., 2018 | ||
| STAT4 | rs7574865 | Kim et al., 2015; Jiang et al., 2016b | ||
| TCF19 | rs1419881 | Kim et al., 2013; Jiang et al., 2015 | ||
| VDR | FokI | He et al., 2018 | ||
| II | HLA | HLA-A | *33:03:01 | Miao et al., 2013 |
| HLA-B | *13:01:01 | Miao et al., 2013 | ||
| HLA-C | Leu-15, rs2853953, rs3130542 | Hu et al., 2013; Jiang et al., 2015; Zhu et al., 2016b | ||
| HLA-DOA | rs378352 | Jiang et al., 2015 | ||
| HLA-DP | rs9366816 | Chang et al., 2014 | ||
| HLA-DPA1 | rs2301220, rs2395309, rs9277341 | Guo et al., 2011; Li et al., 2011a | ||
| HLA-DPB1 | rs9277534, *0201, *0401, *0901, positions 84–87, *0402, *0501, *0201-*0401, *0201-*0402, *0201-*0501, *0401-*0402, *0401-*0501, *0402-*0402, *0402-*0501, *0501-*0501, *0501-*0901, *0501*others, rs9277378, rs10484569, rs3117222, rs9380343, rs3135021, G-A-G-A-T-T1, G-G-G-G-T-C2 | Guo et al., 2011; Thomas et al., 2012; Wong et al., 2013; Zhang et al., 2013e; Hu et al., 2014; Nishida et al., 2014; Nishida et al., 2015; Zhu et al., 2016b | ||
| HLA-DQ | A1*0101-B1*0501, A1*0102-B1*0303, A1*0102-B1*0604, A1*0301-B1*0601, A1*0102-B1*0602, A1*0301-B1*0302, A1*0301-B1*0303, A1*0301-B1*0401, A1*0501-B1*0301 | Mbarek et al., 2011 | ||
| HLA-DQA2 | rs9276370 | Chang et al., 2014 | ||
| HLA-DQB2 | rs7756516 | Chang et al., 2014 | ||
| HLA-DPA1/DPB1 | A-A3, A-A4, T-A-T5,C-A-T6,A1*0103-B1*0401, A1*0103-B1*0402, A1*0202-B1*0301, A1*0202-B1*0501, A-A-C-T7, A-A-C-C//A-G-T-G-C-C8, A-A-C-T//A-G-T-G-C-C9, G-G-T-C//A-G-T-G-C-C10 | Kamatani et al., 2009; Guo et al., 2011; Li et al., 2011a; Wang et al., 2011; Wong et al., 2013 | ||
| HLA-DP/DQ | T-T-G-A-T11, T-T-G-G-T12, carrying 4–6 variant alleles, G-A13, A-G14, A-A15 | Hu et al., 2012; Chang et al., 2014; Al-Qahtani et al., 2014 | ||
| HLA-J | rs400488 | Zhu et al., 2016b | ||
| Cytokines | IL-10RB | rs2834167 | Romporn et al., 2013; Ma et al., 2014 | |
| IL-12B | rs3212227 | He et al., 2015 | ||
| IL-16 | rs11556218 | Li et al., 2011b | ||
| IL-21 | rs2221903 | Li et al., 2013a | ||
| IFN-α2 | p.Ala120Thr | Zhao et al., 2012 | ||
| IFN-αR2 | rs1051393, rs12233338 | Ma et al., 2018a | ||
| IFNLR1 | rs4649203, rs7525481 | Ma et al., 2018a | ||
| IFN-γR1 | rs3799488 | He et al., 2015 | ||
| IFN-γR2 | rs1059293 | He et al., 2015 | ||
| TNF-α | T-C-C-G-G-G16, C-A-C-G-G-G17 | Kim et al., 2003 | ||
| TGF-α | +106151, +103461, A-T-G-T-T-T-T-C-T18 | Kim et al., 2009 | ||
| TLRs | TLR-3 | rs1879026 | Al-Qahtani et al., 2012a | |
| TLR-9 | rs352140 | He et al., 2015 | ||
| MicroRNAs | miR-30a | rs1358379 | Al-Qahtani et al., 2017 | |
| miR-101-2 | rs12375841, T-C19 | Bae et al., 2012 | ||
| miR-122 | rs4309483 | Liu et al., 2014b | ||
| miR-219-1 | rs107822, rs213210, rs421446, C-A-C20, T-G-T21 | Cheong et al., 2013 | ||
| miR-323b | rs56103835 | Yu et al., 2014 | ||
| miR-423 | rs6505162 | Al-Qahtani et al., 2017 | ||
| miR-492 | rs2289030 | Al-Qahtani et al., 2017 | ||
| Others | C2 | p.Glu318Asp, rs7746553, rs9267673, rs9267665, rs9267677, rs9279450, rs10947223 | Zhao et al., 2012; Namgoong et al., 2018 | |
| CD40 | rs1883832 | Jiang et al., 2015 | ||
| CFB | rs12614 | Jiang et al., 2015 | ||
| CTLA-4 | rs3087243, C-A-C-C-G22, T/C-A-C-C-G23, T-A-C-C-A24 | Thio et al., 2004; Chen et al., 2010 | ||
| EHMT2 | rs7887, rs652888, rs35875104, rs41267090 | Jiang et al., 2015; Shin et al., 2017 | ||
| ESR1 | +29 | Deng et al., 2004 | ||
| IFN4/HLA-DQ | rs12971396-rs9275319, rs12971396-rs12979860-rs9275319 | Fan et al., 2016a | ||
| INST10 | rs7000921 | Li et al., 2016 | ||
| KIF1B | A-T-A25 | Al-Qahtani et al., 2012b | ||
| MCP1 | −2518, −2518/−2076(−/ht2), −2518/−2076(ht2/ht2) | Park et al., 2006; Chen et al., 2010 | ||
| MIF | rs755622 | Moudi et al., 2016 | ||
| MxA | −123 | Cao et al., 2009; Rebbani et al., 2017 | ||
| MX1 | rs467960 | He et al., 2015 | ||
| NF-κB | rs2233406, rs3138053 | Zhang et al., 2014a | ||
| NLRX1 | p.Arg707Cys | Zhao et al., 2012 | ||
| NOTCH4 | rs422951 | Jiang et al., 2015 | ||
| NTCP | rs943277, rs4646285 | Wang et al., 2017a; Wu et al., 2018a | ||
| OCT4 | rs13409, rs885952, rs879882, rs1265163, rs2394882, rs3094193, rs3130501, rs3130503, rs3130931, rs3132526, rs3757349, rs9263800, rs117265349 | Shin et al., 2017 | ||
| PAPL | rs423058 | Ma et al., 2014 | ||
| SOCS3 | rs111033850, rs12953258, C-C 26 | Hoan et al., 2017 | ||
| SPP1 | −1800, T-T-C-T-A27 | Shin et al., 2007 | ||
| STAT4 | rs8179673, rs10168266, rs11889341, C-T-C-T-T28 | Jiang et al., 2016b, Lu et al., 2015b | ||
| TMEM2 | p.Ser1254Asn | Zhao et al., 2012 | ||
| TMEM2/IFNA2/NLRX1/C2 | p.Ser1254-Asn/p.Ala120Thr/p.Arg707Cys/p.Glu318Asp | Zhao et al., 2012 | ||
| UBE2L3 | rs2266959, rs4821116 | Liu et al., 2018d, Hu et al., 2013 | ||
| VARS2 | rs1043483, rs1264295, rs2249464, rs2517459, rs2532932, rs9394021, | Cheong et al., 2015 | ||
| ZNRD1 | rs3757328, G-G-A29 | Wen et al., 2015 |
Haplotypes
1G-A-G-A-T-T, rs9277535-rs10484569-rs3128917-rs2281388-rs3117222-rs9380343; 2G-G-G-G-T-C, rs9277535-rs10484569-rs3128917-rs2281388-rs3117222-rs9380343; 3A-A, rs3077-rs9277535; 4A-A, rs2395309-rs9277535; 5T-A-T, rs3077-rs9277378-rs3128917; 6C-A-T, rs3077-rs9277378-rs3128917; 7A-A-C-T, rs2395309-rs3077-rs2301220-rs9277341; 8A-A-C-C//A-G-T-G-C-C, rs2395309-rs3077-rs2301220-rs9277341//rs9277535-rs10484569-rs3128917 -rs2281388-rs3117222-rs9380343; 9A-A-C-T//A-G-T-G-C-C, rs2395309-rs3077-rs2301220-rs9277341//rs9277535-rs10484569-rs3128917 -rs2281388-rs3117222-rs9380343; 10G-G-T-C//A-G-T-G-C-C, rs2395309-rs3077-rs2301220-rs9277341//rs9277535-rs10484569-rs3128917 -rs2281388-rs3117222-rs9380343; 11T-T-G-A-T, rs9276370-rs7756516-rs7453920-rs9277535-rs9366816; 12T-T-G-G-T, rs9276370-rs7756516-rs7453920-rs9277535-rs9366816; 13G-A, rs2856718- rs9275572; 14A-G, rs2856718- rs9275572; 15A-A, rs2856718- rs9275572; 16T-C-C-G-G-G, -1031/-863/-857/-308/-238/-163; 17C-A-C-G-G-G, -1031/-863/-857/-308/-238/-163; 18A-T-G-T-T-T-T-C-T, +88344/+102906/+103432/+103437/+103461/+104261/+104802/+106151/+106318; 19T-C, rs12375841-rs17803780; 20C-A-C, rs421446-rs107822-rs213210; 21T-G-T, rs421446-rs107822-rs213210; 22C-A-C-C-G, -1722/-1661/-658/-319/+49; 23T/C-A-C-C-G, -1722/-1661/-658/-319/+49; 24T-A-C-C-A, -1722/-1661/-658/-319/+49; 25A-T-A, rs17401966-rs12734551-rs3748578; 26C-C, rs111033850-rs12953258; 27T-T-C-T-A, -1800/-1627/+4645/+5806/+6139; 28C-T-C-T-T, rs8179673-rs7574865-rs4274624-rs11889341-rs10168266; 29G-G-A, rs3757328-rs6940552-rs9261204.