TY - JOUR
T1 - Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population
AU - Angulo-Aguado, Mariana
AU - Corredor-Orlandelli, David
AU - Carrillo-Martínez, Juan Camilo
AU - Gonzalez-Cornejo, Mónica
AU - Pineda-Mateus, Eliana
AU - Rojas, Carolina
AU - Triana-Fonseca, Paula
AU - Contreras Bravo, Nora Constanza
AU - Morel, Adrien
AU - Parra Abaunza, Katherine
AU - Restrepo, Carlos M.
AU - Fonseca-Mendoza, Dora Janeth
AU - Ortega-Recalde, Oscar
N1 - Publisher Copyright:
Copyright © 2022 Angulo-Aguado, Corredor-Orlandelli, Carrillo-Martínez, Gonzalez-Cornejo, Pineda-Mateus, Rojas, Triana-Fonseca, Contreras Bravo, Morel, Parra Abaunza, Restrepo, Fonseca-Mendoza and Ortega-Recalde.
PY - 2022/6/20
Y1 - 2022/6/20
N2 - Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2–26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79–0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
AB - Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2–26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79–0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
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U2 - 10.3389/fmed.2022.910098
DO - 10.3389/fmed.2022.910098
M3 - Article
C2 - 35795626
AN - SCOPUS:85133570065
SN - 2296-858X
VL - 9
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 910098
ER -
