Dados do Trabalho

Título

Polymorphisms in ACE1, TMRPSS2 and IFIH1 genes are associated with risk to COVID-19 severity in women

Fundamentação/ Introdução

Although advanced age and presence of comorbidities significantly impact the variation observed in the clinical symptoms of COVID-19, it has been suggested that genetic variants may also be involved in the disease. In this context, some studies have shown genetic polymorphisms contribute to the susceptibility and/or severity of COVID-19; however, the results are still inconclusive.

Objetivos

To investigate the association between rs2285666/ACE2, rs12329760/TMRPSS2, rs2109069/DPP9, rs2304256/TYK2, rs1990760/IFIH1, rs2236757/IFNAR2, rs3775291/TLR3, rs368234815/IFNL4, and rs1799752/ACE1 polymorphisms and COVID-19 severity.

Delineamento e Métodos

This case-control study was performed using DNA samples from the Biobank of Hospital de Clínicas de Porto Alegre, COVID-19 Collection (https://biobanco-covid-19.hcpa.edu.br/samples). We included 694 patients with COVID-19, classified into 280 inpatients and 414 intensive care unit (ICU) patients. Genotyping of polymorphisms were performed by real-time PCR.

Resultados

: Of the 694 subjects included, 47.1% were women and the mean age was 58.6 ± 15.2 years. In the general sample, the frequencies of the nine polymorphisms analyzed did not differ between groups. Stratification analyses according to gender showed that, in women, the frequency of the T allele of the rs1990760/IFIH1 was 46% in ICU patients and 37% in inpatients (P= 0.030). Moreover, the rs1990760 T/T genotype conferred risk for ICU under recessive and additive models [OR 1.836, 95% CI 1.037 – 3.250 (P= 0.050), and OR 2.048, 95% CI 1.087 – 3.858 (P= 0.038), respectively]. Additionally, frequency of the Ins allele of rs1799752/ACE1 was higher in ICU patients compared to the inpatients (41% vs. 32%, P= 0.018) and the Ins/Ins genotype was associated with risk for more severe forms of COVID-19 under the dominant model (OR 2.283, 95% CI 1.366 – 3.814, P= 0.002). The frequency of the T allele of the rs12329760/TMPRSS2 also differed between inpatients and ICU patients (22% vs. 15%, P= 0.021), and the T/T genotype conferred risk for ICU under the dominant model (OR 1.815, 95% CI 1.135 – 2.901, P= 0.017). Interaction analysis between ACE1, IFIH1 and TMPRSS2 polymorphisms showed that having 4, 5 or 6 minor alleles of these polymorphisms increases the risk of ICU compared to carrying 0 to 3 minor alleles (OR 3.859, 95% CI 1.271 – 11.714, P= 0.017).

Conclusões/ Considerações Finais

The rs1799752/ACE1, rs12329760/TMPRSS2 and rs1990760/IFIH1 polymorphisms are associated with risk for COVID-19 severity in women.

Palavras-Chave

Polymorphisms; COVID-19; Genetic.