严重急性呼吸综合征冠状病毒2型病毒血症的出现与新冠病毒疾病发病机制相关基因的遗传变异有关。

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

作者信息

Roy-Vallejo Emilia, Fernández De Córdoba-Oñate Sara, Delgado-Wicke Pablo, Triguero-Martínez Ana, Montes Nuria, Carracedo-Rodríguez Rosa, Zurita-Cruz Nelly, Marcos-Jiménez Ana, Lamana Amalia, Galván-Román José María, Villapalos García Gonzalo, Zubiaur Pablo, Ciudad Marianela, Rabes Laura, Sanz Marta, Rodríguez Carlos, Villa Almudena, Rodríguez Jesús Álvarez, Marcos Celeste, Hernando Julia, Díaz-Fernández Paula, Abad Francisco, de Los Santos Ignacio, Rodríguez Serrano Diego A, García-Vicuña Rosario, Suárez Fernández Carmen, P Gomariz Rosa, Muñoz-Calleja Cecilia, Fernández-Ruiz Elena, González-Álvaro Isidoro, Cardeñoso Laura, Barrios Ana, Sanz Jesús, Casado Pedro, Gutiérrez Ángela, Bautista Azucena, Hernández Pilar, Ruiz Giménez Nuria, Moyano Berta, Gil Paloma, Jesús Delgado María, Parra Pedro, Sánchez Beatriz, Sáez Carmen, Fernández Rico Marta, Arévalo Román Cristina, Castañeda Santos, Llorente Irene, G Tomero Eva, García Castañeda Noelia, Uriarte Miren, Fontán García-Rodrigo Leticia, Domingo García Diego, Alarcón Cavero Teresa, Auxiliadora Semiglia Chong María, Gutiérrez Cobos Ainhoa, Sánchez-Madrid Francisco, Martín Gayo Enrique, Sánchez-Cerrillo Ildefonso, Martínez-Fleta Pedro, López-Sanz Celia, Gabrie Ligia, Del Campo Guerola Luciana, Tejedor Reyes, Ancochea Julio, García Castillo Elena, Ávalos Elena, Sánchez-Azofra Ana, Alonso Tamara, Cisneros Carolina, Valenzuela Claudia, Javier García Pérez Francisco, María Girón Rosa, Aspa Javier, Marcos Celeste, Del Perpetuo Socorro Churruca M, Zamora Enrique, Martínez Adrián, Barrio Mayo Mar, Henares Espi Rosalina, Méndez Rosa, Arribas David, Chicot Llano Marta, González Begoña, Quicios Begoña, Patiño Pablo, Trigueros Marina, Dominguez Peña Cristina, Jiménez Jiménez David, Villamayor Pablo, Canabal Alfonso, de la Cámara Rafael, Ortiz Javier, Iturrate Isabel

机构信息

Internal Medicine Department, Hospital Universitario La Princesa, Madrid, Spain.

Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.

出版信息

Front Med (Lausanne). 2023 Sep 22;10:1215246. doi: 10.3389/fmed.2023.1215246. eCollection 2023.

Abstract

INTRODUCTION

SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity.

MATERIALS AND METHODS

Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed.

RESULTS

The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (; T/T genotype OR 9.9  < 0.0001), rs78958998 (probably associated with expression; A/T genotype OR 2.3,  = 0.04 and T/T genotype OR 12.9,  < 0.0001), and rs713400 (eQTL for ; C/T + T/T genotype OR 1.86,  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3,  = 0.01), rs2660 (; A/G genotype OR 0.6,  = 0.08), rs896 (; T/T genotype OR 0.4,  = 0.02) and rs33980500 (; C/T + T/T genotype OR 0.3,  = 0.01) were associated with lower risk of viremia.

CONCLUSION

Genetic variants in (rs2071746), (rs78958998), (rs713400), (rs11052877), (rs33980500), (rs2660) and (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

摘要

引言

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒载量与2019冠状病毒病(COVID-19)的严重程度相关。本研究的主要目的是评估SARS-CoV-2病毒血症与我们团队之前作为COVID-19严重程度预测指标研究过的基因中的单核苷酸多态性(SNP)之间的关系。

材料与方法

回顾性观察研究,纳入2020年3月至2021年12月期间在拉公主大学医院因COVID-19住院且至少进行过一次病毒血症测定的340例患者。当病毒载量高于可定量阈值(20拷贝/毫升)时,视为病毒血症阳性。共对38个SNP进行基因分型。为研究它们与病毒血症的关联,进行了多因素逻辑回归分析。

结果

研究人群的平均年龄为64.5岁(标准差16.6),60.9%的患者为男性,79.4%为非西班牙裔白人。只有126例患者(37.1%)至少有一次病毒血症阳性。在对混杂因素进行调整后,rs2071746的次要等位基因(;T/T基因型比值比[OR]为9.9,<0.0001)、rs78958998(可能与表达相关;A/T基因型OR为2.3,=0.04,T/T基因型OR为12.9,<0.0001)和rs713400(的表达数量性状位点[ eQTL];C/T + T/T基因型OR为1.86,=0.10)与病毒血症风险较高相关,而rs11052877的次要等位基因(;A/G基因型OR为0.5,p = 0.04,G/G基因型OR为0.3,=0.01)、rs2660(;A/G基因型OR为0.6,=0.08)、rs896(;T/T基因型OR为0.4,=0.02)和rs33980500(;C/T + T/T基因型OR为0.3,=0.01)与病毒血症风险较低相关。

结论

(rs2071746)、(rs78958998)、(rs713400)、(rs11052877)、(rs33980500)、(rs2660)和(rs896)中的基因变异可以解释我们研究人群中SARS-CoV-2病毒血症的异质性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/973b/10557488/e01ed341566b/fmed-10-1215246-g001.jpg

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