重症新型冠状病毒肺炎患者遗传易感性研究进展

doi:10.16288/j.yczz.22-058

遗传 ›› 2022, Vol. 44 ›› Issue (8): 672-681.doi: 10.16288/j.yczz.22-058

重症新型冠状病毒肺炎患者遗传易感性研究进展

刘文兵^1,²(), 刘丹¹, 闫进¹, 刘欣^1,², 王前飞^1,²()

1. 中国科学院北京基因组研究所(国家生物信息中心),中国科学院精准基因组医学重点实验室,北京 100101
2. 中国科学院大学,北京 100049

收稿日期:2022-03-06 修回日期:2022-05-25 出版日期:2022-08-20 发布日期:2022-06-10
通讯作者: 王前飞 E-mail:liuwenbing@big.ac.cn;wangqf@big.ac.cn
作者简介:刘文兵,在读博士研究生,研究方向：遗传学。E-mail: liuwenbing@big.ac.cn
基金资助:
北京市自然科学基金资助项目编号(M21022)

Genetic predisposition in patients with severe COVID-19

Wenbing Liu^1,²(), Dan Liu¹, Jin Yan¹, Xin Liu^1,², Qianfei Wang^1,²()

1. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing 100101, China
2. University of Chinese Academy of Sciences, Beijing 100049, China

Received:2022-03-06 Revised:2022-05-25 Online:2022-08-20 Published:2022-06-10
Contact: Wang Qianfei E-mail:liuwenbing@big.ac.cn;wangqf@big.ac.cn
Supported by:
Beijing Natural Science Foundation(M21022)

摘要/Abstract

摘要：

新型冠状病毒肺炎是由新型冠状病毒感染引起的全球大流行疾病。患者呈现出无症状感染、轻症到(危)重症不同严重程度的临床表现。部分重症患者因发生细胞因子风暴而出现多器官功能衰竭并最终导致死亡。除性别、年龄、基础疾病(如高血压、糖尿病)等增加重型感染风险外,宿主先天遗传缺陷也被认为与疾病严重程度(包括细胞因子风暴的发生)密切相关。在重症患者中,相继发现与病毒识别、杀伤等相关的关键基因(如TLR7、UNC13D等)先天遗传变异。本文主要总结了宿主抗病毒免疫应答机制及与新型冠状病毒感染严重程度相关的先天变异基因,以期为新型冠状病毒肺炎的早期干预和分层治疗提供遗传学依据。

关键词: 重症新型冠状病毒肺炎患者, 先天遗传变异, 免疫缺陷

Abstract:

The coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. COVID-19 has a variety of clinical manifestations, ranging from asymptomatic infection or mild symptoms to severe symptoms. Severe COVID-19 patients experience cytokine storm, resulting in multi-organ failure and even death. Male gender, old age, and pre-existing comorbidities (such as hypertension and diabetes ) are risk factors for COVID-19 severity. Recently, a series of studies suggested that genetic defects might also be related to disease severity and the cytokine storm occurence. Genetic variants in key viral immune genes, such as TLR7 and UNC13D, have been identified in severe COVID-19 patients from previous reports. In this review, we summarize the mechanisms underlying immune responses against SARS-CoV-2 and genetic variants that associated with the severity of COVID-19. The study of genetic basis of COVID-19 will be of great benefit for early disease detection and intervention.

Key words: severe COVID-19 patients, germline variants, immunodeficiency

刘文兵, 刘丹, 闫进, 刘欣, 王前飞. 重症新型冠状病毒肺炎患者遗传易感性研究进展[J]. 遗传, 2022, 44(8): 672-681.

Wenbing Liu, Dan Liu, Jin Yan, Xin Liu, Qianfei Wang. Genetic predisposition in patients with severe COVID-19[J]. Hereditas(Beijing), 2022, 44(8): 672-681.

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参考文献 49

[1]	Lu RJ, Zhao X, Li J, Niu PH, Yang B, Wu HL, Wang WL, Song H, Huang BY, Zhu N, Bi YH, Ma XJ, Zhan FX, Wang L, Hu T, Zhou H, Hu ZH, Zhou WM, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan JY, Xie ZH, Ma JM, Liu WJ, Wang DY, Xu WB, Holmes EC, Gao GF, Wu GZ, Chen WJ, Shi WF, Tan WJ. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224): 565-574. doi: 10.1016/S0140-6736(20)30251-8
[2]	Shamsi A, Mohammad T, Anwar S, Amani S, Khan MS, Husain FM, Rehman MT, Islam A, Hassan MI. Potential drug targets of SARS-CoV-2: from genomics to therapeutics. Int J Biol Macromol, 2021, 177: 1-9. doi: 10.1016/j.ijbiomac.2021.02.071 pmid: 33577820
[3]	Xia XH. Domains and functions of spike protein in SRAS-COV-2 in the context of vaccine design. Viruses, 2021, 13(1): 109. doi: 10.3390/v13010109
[4]	Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for COVID-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020, 382(18): 1708-1720. doi: 10.1056/NEJMoa2002032
[5]	Wang DW, Hu B, Hu C, Zhu FF, Liu X, Zhang J, Wang BB, Xiang H, Cheng ZS, Xiong Y, Zhao Y, Li YR, Wang XH, Peng ZY.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11): 1061-1069. doi: 10.1001/jama.2020.1585
[6]	Jouanguy E, Béziat V, Mogensen TH, Casanova JL, Tangye SG, Zhang SY. Human inborn errors of immunity to herpes viruses. Curr Opin Immunol, 2020, 62: 106-122. doi: 10.1016/j.coi.2020.01.004
[7]	Samavati L, Uhal BD.ACE2, much more than just a receptor for SARS-COV-2. Front Cell Infect Microbiol, 2020, 10: 317. doi: 10.3389/fcimb.2020.00317
[8]	Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2): 271-280.e8. doi: S0092-8674(20)30229-4 pmid: 32142651
[9]	Cavalcante-Silva LHA, Carvalho DCM, Lima ÉA, Galvão JGFM, da Silva JSF, Sales-Neto JM, Rodrigues-Mascarenhas S. Neutrophils and COVID-19: the road so far. Int Immunopharmacol, 2021, 90: 107233. doi: 10.1016/j.intimp.2020.107233
[10]	Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol, 2020, 38(1): 1-9.
[11]	Solimani F, Meier K, Ghoreschi K. Janus kinase signaling as risk factor and therapeutic target for severe SARS- CoV-2 infection. Eur J Immunol, 2021, 51(5): 1071-1075. doi: 10.1002/eji.202149173 pmid: 33675065
[12]	Cox RJ, Brokstad KA.Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol, 2020, 20(10): 581-582. doi: 10.1038/s41577-020-00436-4
[13]	Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol, 2020, 11: 1446. doi: 10.3389/fimmu.2020.01446 pmid: 32612617
[14]	Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol, 2017, 39(5): 529-539. doi: 10.1007/s00281-017-0629-x pmid: 28466096
[15]	Huang CL, Wang YM, Li XW, Ren LL, Zhao JP, Hu Y, Zhang L, Fan GH, Xu JY, Gu XY, Cheng ZS, Yu T, Xia JA, Wei Y, Wu WJ, Xie XL, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie JG, Wang GF, Jiang RM, Gao ZC, Jin Q, Wang JW, Cao B.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223): 497-506. doi: 10.1016/S0140-6736(20)30183-5
[16]	Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis, 2021, 40(5): 905-919.
[17]	Devaux CA, Rolain JM, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect, 2020, 53(3): 425-435. doi: 10.1016/j.jmii.2020.04.015
[18]	Horowitz JE, Kosmicki JA, Damask A, Sharma D, Roberts GHL, Justice AE, Banerjee N, Coignet MV, Yadav A, Leader JB, Marcketta A, Park DS, Lanche R, Maxwell E, Knight SC, Bai X, Guturu H, Sun D, Baltzell A, Kury FSP, Backman JD, Girshick AR, O'Dushlaine C, McCurdy SR, Partha R, Mansfield AJ, Turissini DA, Li AH, Zhang M, Mbatchou J, Watanabe K, Gurski L, McCarthy SE, Kang HM, Dobbyn L, Stahl E, Verma A, Sirugo G, Regeneron Genetics C, Ritchie MD, Jones M, Balasubramanian S, Siminovitch K, Salerno WJ, Shuldiner AR, Rader DJ, Mirshahi T, Locke AE, Marchini J, Overton JD, Carey DJ, Habegger L, Cantor MN, Rand KA, Hong EL, Reid JG, Ball CA, Baras A, Abecasis GR, Ferreira MA. Genome- wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease. MedRxiv, 2021.
[19]	Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A, Doddato G, Giliberti A, Marconi C, Musacchia F, Pippucci T, Torella A, Trezza A, Valentino F, Baldassarri M, Brusco A, Asselta R, Bruttini M, Furini S, Seri M, Nigro V, Matullo G, Tartaglia M, Mari F, Study G-CM, Renieri A, Pinto AM. ACE 2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet, 2020, 28(11): 1602-1614. doi: 10.1038/s41431-020-0691-z
[20]	Andolfo I, Russo R, Lasorsa VA, Cantalupo S, Rosato BE, Bonfiglio F, Frisso G, Abete P, Cassese GM, Servillo G, Esposito G, Gentile I, Piscopo C, Villani R, Fiorentino G, Cerino P, Buonerba C, Pierri B, Zollo M, Iolascon A, Capasso M.Common variants at 21q22.3 locus influence MX1 and TMPRSS 2 gene expression and susceptibility to severe COVID-19. iScience, 2021, 24(4): 102322. doi: 10.1016/j.isci.2021.102322
[21]	Wang F, Huang SJ, Gao RS, Zhou YW, Lai CX, Li ZC, Xian WJ, Qian XB, Li ZY, Huang YS, Tang QY, Liu PH, Chen RK, Liu R, Li X, Tong X, Zhou X, Bai Y, Duan G, Zhang T, Xu X, Wang J, Yang HM, Liu SY, He Q, Jin X, Liu L. Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility. Cell Discov, 2020, 6(1): 83. doi: 10.1038/s41421-020-00231-4
[22]	Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY), 2020, 12(11): 10087-10098.
[23]	Dean L. ABO blood group. In: PrattVM, ScottSA, PirmohamedM, EsquivelB, KaneMS, KattmanBL, MalheiroAJ, editors. MedicalGenetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US), 2012.
[24]	Ewald DR, Sumner SC. Blood type biochemistry and human disease. Wiley Interdiscip Rev Syst Biol Med, 2016, 8(6): 517-535. doi: 10.1002/wsbm.1355
[25]	Liu NY, Zhang TT, Ma LN, Zhang HQ, Wang HC, Wei W, Pei H, Li H. The impact of ABO blood group on COVID-19 infection risk and mortality: a systematic review and meta-analysis. Blood Rev, 2021, 48: 100785. doi: 10.1016/j.blre.2020.100785
[26]	Zhao J, Yang Y, Huang H, Li D, Gu DF, Lu XF, Zhang Z, Liu L, Liu T, Liu YK, He YJ, Sun B, Wei ML, Yang GY, Wang XH, Zhang L, Zhou XY, Xing MZ, Wang PG. Relationship between the ABO blood group and the coronavirus disease 2019(COVID-19) susceptibility. Clin Infect Dis, 2021, 73(2): 328-331. doi: 10.1093/cid/ciaa1150
[27]	Severe Covid GG, Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernández J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kässens J, May S, Wendorff M, Wienbrandt L, Uellendahl- Werth F, Zheng TH, Yi XL, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julià A, Pesenti A, Voza A, Jiménez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestaña D, Muñiz-Diaz E, Sandoval E, Paraboschi EM, Navas E, García Sánchez F, Ceriotti F, Martinelli- Boneschi F, Peyvandi F, Blasi F, Téllez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galván-Femenia I, Martín J, Erdmann J, Ferrusquía- Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Rühlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta- Herrera M, D'Angiò M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodríguez-Gandía M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martínez N, Özer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gómez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A, Karlsen TH. Genomewide association study of severe covid-19 with respiratory failure. N Engl J Med, 2020, 383(16): 1522-1534. doi: 10.1056/NEJMoa2020283
[28]	Shibeeb S, Khan A. ABO blood group association and COVID-19. COVID-19 susceptibility and severity: a review. Hematol Transfus Cell Ther, 2022, 44(1): 70-75. doi: 10.1016/j.htct.2021.07.006
[29]	Dai XF. ABO blood group predisposes to COVID-19 severity and cardiovascular diseases. Eur J Prev Cardiol, 2020, 27(13): 1436-1437. doi: 10.1177/2047487320922370
[30]	Dendrou CA, Petersen J, Rossjohn J, Fugger L. HLA variation and disease. Nat Rev Immunol, 2018, 18(5): 325-339. doi: 10.1038/nri.2017.143
[31]	Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez- Fuertes M, Wang XM, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Poller W, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine, 2021, 40: 101099. doi: 10.1016/j.eclinm.2021.101099
[32]	Novelli A, Andreani M, Biancolella M, Liberatoscioli L, Passarelli C, Colona VL, Rogliani P, Leonardis F, Campana A, Carsetti R, Andreoni M, Bernardini S, Novelli G, Locatelli F. HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients. HLA, 2020, 96(5): 610-614. doi: 10.1111/tan.14047
[33]	Sa Ribero M, Jouvenet N, Dreux M, Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog, 2020, 16(7): e1008737. doi: 10.1371/journal.ppat.1008737
[34]	van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, van Deuren RC, Steehouwer M, van Reijmersdal SV, Jaeger M, Hofste T, Astuti G, Corominas Galbany J, van der Schoot V, van der Hoeven H, Hagmolen Of Ten Have W, Klijn E, van den Meer C, Fiddelaers J, de Mast Q, Bleeker-Rovers CP, Joosten LAB, Yntema HG, Gilissen C, Nelen M, van der Meer JWM, Brunner HG, Netea MG, van de Veerdonk FL, Hoischen A. Presence of genetic variants among young men with severe COVID-19. JAMA, 2020, 324(7): 663-673.
[35]	Zhang Q, Bastard P, Liu ZY, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye JQ, Bolze A, Bigio B, Yang R, Arias AA, Zhou QH, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/ TAGC COVID Immunity Group, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 2020, 370(6515): eabd4570. doi: 10.1126/science.abd4570
[36]	Hu BY, Huang SY, Yin LH.The cytokine storm and COVID-19. J Med Virol, 2021, 93(1): 250-256. doi: 10.1002/jmv.26232
[37]	Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol, 2017, 39(5): 517-528. doi: 10.1007/s00281-017-0639-8 pmid: 28555385
[38]	Ye Q, Wang BL, Mao JH.The pathogenesis and treatment of the `cytokine storm' in COVID-19. J Infect, 2020, 80(6): 607-613. doi: 10.1016/j.jinf.2020.03.037
[39]	Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Tang MLK, Tangye SG, Torgerson TR, Casanova JL, Sullivan KE. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol, 2018, 38(1): 129-143. doi: 10.1007/s10875-017-0465-8
[40]	Canna SW, Marsh RA. Pediatric hemophagocytic lymphohistiocytosis. Blood, 2020, 135(16): 1332-1343. doi: 10.1182/blood.2019000936
[41]	Luo H, Liu D, Liu WB, Wang GX, Chen LT, Cao Y, Wei J, Xiao M, Liu X, Huang G, Wang W, Zhou JF, Wang QF. Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms. Eur J Hum Genet, 2021, 29(8): 1312-1315. doi: 10.1038/s41431-021-00886-x
[42]	Cotsapas C, Saarela J, Farmer JR, Scaria V, Abraham RS.Do monogenic inborn errors of immunity cause susceptibility to severe COVID-19? J Clin Invest, 2021, 131(14): e149459. doi: 10.1172/JCI149459
[43]	Ren XW, Wen W, Fan XY, Hou WH, Su B, Cai PF, Li JS, Liu Y, Tang F, Zhang F, Yang Y, He JP, Ma WJ, He JJ, Wang PP, Cao QQ, Chen FJ, Chen YQ, Cheng XL, Deng GH, Deng XL, Ding WY, Feng YM, Gan R, Guo C, Guo WQ, He S, Jiang C, Liang JR, Li YM, Lin J, Ling Y, Liu HF, Liu JW, Liu NP, Liu SQ, Luo M, Ma Q, Song QB, Sun WJN, Wang GX, Wang F, Wang Y, Wen XF, Wu Q, Xu G, Xie XW, Xiong XX, Xing XD, Xu H, Yin CH, Yu DD, Yu KZ, Yuan J, Zhang B, Zhang PP, Zhang T, Zhao JC, Zhao PD, Zhou JF, Zhou W, Zhong SJ, Zhong XS, Zhang SY, Zhu L, Zhu P, Zou B, Zou JH, Zuo ZT, Bai F, Huang X, Zhou PH, Jiang QH, Huang ZW, Bei JX, Wei L, Bian XW, Liu XD, Cheng T, Li XP, Zhao PS, Wang FS, Wang HY, Su B, Zhang Z, Qu K, Wang XQ, Chen JK, Jin RH, Zhang ZM. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell, 2021, 184(7): 1895-913.e19. doi: 10.1016/j.cell.2021.01.053
[44]	Callaway E. Beyond Omicron: what’s next for COVID’s viral evolution. Nature, 2021, 600(7888): 204-207. doi: 10.1038/d41586-021-03619-8
[45]	Phillips N. The coronavirus is here to stay — here’s what that means. Nature, 2021, 590(7846): 382-384. doi: 10.1038/d41586-021-00396-2
[46]	Maslo C, Friedland R, Toubkin M, Laubscher A, Akaloo T, Kama B. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves. JAMA, 2022, 327(6): 583-584. doi: 10.1001/jama.2021.24868
[47]	Murray CJL. COVID-19 will continue but the end of the pandemic is near. Lancet, 2022, 399(10323): 417-419. doi: 10.1016/S0140-6736(22)00100-3
[48]	Wolter N, Jassat W, Walaza S, Welch R, Moultrie H, Groome M, Amoako DG, Everatt J, Bhiman JN, Scheepers C, Tebeila N, Chiwandire N, du Plessis M, Govender N, Ismail A, Glass A, Mlisana K, Stevens W, Treurnicht FK, Makatini Z, Hsiao NY, Parboosing R, Wadula J, Hussey H, Davies MA, Boulle A, von Gottberg A, Cohen C. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study. Lancet, 2022, 399(10323): 437-446. doi: 10.1016/S0140-6736(22)00017-4
[49]	Carter-Timofte ME, Jørgensen SE, Freytag MR, Thomsen MM, Brinck Andersen NS, Al-Mousawi A, Hait AS, Mogensen TH.Deciphering the role of host genetics in susceptibility to severe COVID-19. Front Immunol, 2020, 11: 1606. doi: 10.3389/fimmu.2020.01606 pmid: 32695122

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分类	基因	突变/多态性	突变表型	参考文献
病毒入侵	ACE2	rs190509934	降低表达	[18]
病毒入侵	ACE2	rs41303171	预测影响蛋白结构	[19]
病毒入侵	TMPRSS2	rs12329760	预测影响蛋白结构	[20~22]
血型系统	ABO	rs657152	无相关报道	[27]
HLA	HLA-A	HLA-A*11:01	无相关报道	[21]
HLA	HLA-B	HLA-B*51:01	无相关报道	[21]
HLA	HLA-C	HLA-C*14:02	无相关报道	[21]
HLA	HLA-DRB1	HLA-DRB1*14:04	无相关报道	[21]
HLA	HLA-DQA1	HLA-DQA1*01:01	无相关报道	[21]
HLA	HLA-C	HLA-C*04:01	无相关报道	[31]
HLA	HLA-DRB1	HLA-DRB1*15:01	无相关报道	[32]
HLA	HLA-DQB1	HLA-DQB1*06:02	无相关报道	[32]
HLA	HLA-B	HLA-B*27:07	无相关报道	[32]
干扰素通路	TLR7	c.2129_2132del;p.(Gln710Argfs*18)	降低表达	[34]
干扰素通路	TLR7	c.2383G>T;p.(Val795Phe)	降低表达	[34]
炎症因子风暴	UNC13D	c.2588G?>?A:p.(Gly863Asp)	预测影响蛋白结构	[41]
炎症因子风暴	AP3B1	c.2779G?>?A:p.(Gly927Ser)	预测影响蛋白结构	[41]
炎症因子风暴	AP3B1	c.911?C?>?T:p.(Thr304Ile)	预测影响蛋白结构	[41]

重症新型冠状病毒肺炎患者遗传易感性研究进展

Genetic predisposition in patients with severe COVID-19

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[1]	韩英伦, 李庆伟. CRISPR/Cas9基因组编辑技术在HIV-1感染治疗中的应用进展[J]. 遗传, 2016, 38(1): 9-16.
[2]	赵建元,丁寄葳,米泽云,周金明,魏涛,岑山. HIV-1初始传播病毒Vpr基因遗传变异对诱导G₂期阻滞及细胞凋亡的影响[J]. 遗传, 2015, 37(5): 480-486.
[3]	钱源，孙浩，林克勤，史磊，史荔，褚嘉祐. CCR2-64Ⅰ在中国南方14个少数民族群体中的分布[J]. 遗传, 2008, 30(3): 321-323.
[4]	叶峻杰，王福生，彭林，金磊，丁明，刘明旭. 中国傣族、景颇族人群中与艾滋病相关的CCR5△32、CCR2b-64I、SDF1-3′A等位基因多态性分布[J]. 遗传, 2003, 25(6): 655-659.