Gutiérrez-Pérez Ilse Adriana, Buendía-Roldán Ivette, Zaragoza-García Oscar, Pérez-Rubio Gloria, Villafan-Bernal José Rafael, Chávez-Galán Leslie, Parra-Rojas Isela, Hernández-Zenteno Rafael de Jesús, Fricke-Galindo Ingrid, Castro-Alarcón Natividad, Bautista-Becerril Brandon, Falfán-Valencia Ramcés, Guzmán-Guzmán Iris Paola
Faculty of Chemical-Biological Sciences, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, 39000, Mexico.
Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico.
Heliyon. 2024 Mar 15;10(6):e27997. doi: 10.1016/j.heliyon.2024.e27997. eCollection 2024 Mar 30.
Enzymes of the peptidylarginine deiminase family (PADs) play a relevant role in the pathogenesis of COVID-19. However, the association of single nucleotide polymorphisms (SNPs) in their genes with COVID-19 severity and death is unknown.
We included 1045 patients who were diagnosed with COVID-19 between October 2020 and December 2021. All subjects were genotyped for (rs1005753 and rs2235926) and (rs11203366, rs11203367, and rs874881) SNPs by TaqMan assays and their associations with disease severity, death, and inflammatory biomarkers were evaluated.
291 patients presented had severe COVID-19 according to PaO/FiO, and 393 had a non-survival outcome. Carriers of the rs1005753 G/G genotype in the gene presented susceptibility for severe COVID-19, while the heterozygous carriers in rs11203366, rs11203367, and rs874881 of the gene showed risk of death. The GTACC haplotype in - was associated with susceptibility to severe COVID-19, while the GCACC haplotype was a protective factor. The GCGTG haplotype was associated with severe COVID-19 but as a protective haplotype for death. Finally, the GTACC haplotype was associated with platelet-to-lymphocyte ratio (PLR), the GCACC haplotype with neutrophil-to-hemoglobin and lymphocyte and the GCGTG haplotype as a protective factor for the elevation of procalcitonin, D-dimer, CRP, LCRP, NHL, SII, NLR, and PLR.
Our results suggest that the haplotypic combination of GTACC and some individual genotypes of and contribute to the subjects' susceptibility for severity and death by COVID-19.
肽基精氨酸脱亚氨酶家族（PADs）的酶在新冠病毒病（COVID-19）发病机制中起相关作用。然而，其基因中的单核苷酸多态性（SNP）与COVID-19严重程度及死亡之间的关联尚不清楚。
我们纳入了2020年10月至2021年12月期间被诊断为COVID-19的1045例患者。通过TaqMan分析对所有受试者进行 （rs1005753和rs2235926）以及 （rs11203366、rs11203367和rs874881）SNP基因分型，并评估它们与疾病严重程度、死亡及炎症生物标志物的关联。
根据氧合指数（PaO₂/FiO₂），291例患者患有重症COVID-19，393例患者预后不良。 基因中rs1005753 G/G基因型携带者对重症COVID-19易感，而 基因中rs11203366、rs11203367和rs874881的杂合子携带者显示出死亡风险。 - 的GTACC单倍型与重症COVID-19易感性相关，而GCACC单倍型是一个保护因素。GCGTG单倍型与重症COVID-19相关，但作为死亡的保护单倍型。最后，GTACC单倍型与血小板与淋巴细胞比值（PLR）相关，GCACC单倍型与中性粒细胞与血红蛋白及淋巴细胞相关，GCGTG单倍型作为降钙素原、D-二聚体、C反应蛋白（CRP）、白细胞介素-6（LCRP）、非高密度脂蛋白胆固醇（NHL）、全身炎症反应指数（SII）、中性粒细胞与淋巴细胞比值（NLR）和PLR升高的保护因素。
我们的结果表明，GTACC的单倍型组合以及 和 的一些个体基因型导致受试者对COVID-19的严重程度和死亡易感。
