Impact of the ABCB1 Drug Resistance Gene on the Risk Factors of Patients with COVID-19 and Its Relationship with the Drugs Used

Abstract

Objective

In the last two years progress was made in molecular, physio pathological understanding and the form of transmission of COVID-19, and different therapeutic strategies have been explored to deal with the situation of the pandemic. However, the evaluation of certain genes that participate in the metabolism and transport of these drugs has not been fully explored. A lack of response to treatment and a lower survival have been observed that may be due to the presence of the ABCB1 drug resistance gene. Our research group analyzed whether the expression levels of the ABCB1 gene are associated with comorbidities, treatments, overall survival and risk of death in patients with severe COVID-19.

Methods

The expression levels of the ABCB1 gene were analyzed by RT-qPCR in 61 patients diagnosed with COVID-19. The association between the levels of expression, the risk variables and different treatments were determined by the Chi-Square test and the Fisher’s exact test. Global Survival (GS) was determined by the Kaplan–Meier method. The impact of high levels of expression and the risk of death was performed by odds ratio.

Results

The different risk variables showed that patients with either high or absent levels of ABCB1 gene expression presented a greater risk of death (OR 3.08, 95%, CI 1.02–9.26) as well as need for ventilatory support (OR 2.8, 95%, CI 0.98 −8.5). Patients with diabetes and COVID-19, treated with metformin, were associated with a lower risk of death (OR 1.11, 95%, CI 0.38–3.22). OS with respect to high or absent levels of expression of the ABCB1 gene was lower.

Conclusion

High levels or null expression of the ABCB1 gene are associated with a higher risk of death or progression of the disease, the use of metformin in patients with COVID-19 confers a lower risk of death.

Keywords:

• ABCB1
• SARS-CoV2
• drug transporter genes

Abbreviations

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; ABCB1, ATP-binding cassette B1; P-gp, P-glycoprotein; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; NF-kB, nuclear factor kappa B; OS, overall survival.

Data Sharing Statement

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

Written informed consent was obtained from all subjects and the study was approved by the Ethics Committee of the Hospital General Mexico “Dr Eduardo Liceaga”.

Acknowledgments

The authors thank Direccion de Investigación Hospital General de Mexico.

Author contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the Direccion de Investigacion Hospital General Mexico “Dr Eduardo Liceaga” (DI/20/204/04/31, DI/20/204/04/41).