Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

被引：53

作者：

Andolfo, Immacolata ^{[1
,2
]}

Russo, Roberta ^{[1
,2
]}

Lasorsa, Vito Alessandro ^{[1
,2
]}

Cantalupo, Sueva ^{[1
,2
]}

Rosato, Barbara Eleni ^{[1
,2
]}

Bonfiglio, Ferdinando ^{[3
]}

Frisso, Giulia ^{[1
,2
]}

Abete, Pasquale ^{[4
]}

Cassese, Gian Marco ^{[4
]}

Servillo, Giuseppe ^{[5
]}

Esposito, Gabriella ^{[1
,2
]}

Gentile, Ivan ^{[6
]}

Piscopo, Carmelo ^{[7
]}

Villani, Romolo ^{[8
]}

Fiorentino, Giuseppe ^{[9
]}

Cerino, Pellegrino ^{[10
]}

Buonerba, Carlo ^{[10
]}

Pierri, Biancamaria ^{[10
,11
]}

Zollo, Massimo ^{[1
,2
]}

Iolascon, Achille ^{[1
,2
]}

Capasso, Mario ^{[1
,2
]}

机构：

[1] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80145 Naples, Italy

[2] CEINGE Biotecnol Avanzate, Via Gaetano Salvatore 486, I-80145 Naples, Italy

[3] Univ Napoli Federico II, Dipartimento Ingn Chim Mat & Prod Ind, Naples, Italy

[4] COVID Hosp, POS Anna & SS Madonna Neve Boscotrecase, Osped Riuniti Area Vesuviana, Naples, Italy

[5] Univ Napoli Federico II, Dipartimento Neurosci & Sci Riprodutt Odontostoma, Naples, Italy

[6] Univ Napoli Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy

[7] AORN Antonio Cardarelli, Med & Lab Genet Unit, Naples, Italy

[8] AORN Antonio Cardarelli, Poison Ctr, Naples, Italy

[9] AORN Colli Presidio Osped Cotugno, Naples, Italy

[10] Ist Zooprofilatt Sperimentale Mezzogiorno, Naples, Italy

[11] Univ Salerno, Scuola Med Salernitana, Dipartimento Med Chirurg & Odontoiatria, Baronissi, Italy

来源：

ISCIENCE | 2021年 / 24卷 / 04期

关键词：

SPIKE PROTEIN; SARS-COV-2;

D O I：

10.1016/j.isci.2021.102322

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.EY

引用

页数：27

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