Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population

Abstract

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.

Dataset of single nucleotide polymorphisms of immune-associated genes in patients with SARS-CoV-2 infection

“…Since the beginning of the pandemic, several manuscripts have been published on risk factors associated with a mild versus a severe course of infection with SARS-CoV-2 [31][32][33][34][35]. Our limited sample size did not allow any definitive conclusions on genetic risk factors such as ABO or HLA type directly influencing clinical course.…”

Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population

“…The biological basis of clinical variables has been discussed in previous models and reviews [123][124][125] . On the other hand, recent studies have integrated specific genetic variants into predictive models 38,126 . It is to be noted that the inclusion of variants from the IL1RN and KANSL1 genes in our model represents a novel approach.…”

Persistent Neurocognitive Problems Related to COVID-19 in Children and Adolescents

“…When examining genetic susceptibility to the symptoms of post-COVID-19 until March 2022, no studies were found that explored the potential link among them (18). A recent study conducted on seropositive adult patients with asymptomatic/ mild disease reported that rs11385942 polymorphism of the leucine zipper transcription factor like 1 gene (coding a protein involved in the primary cilia function and the immunological synapse between T-cells and antigen-presenting cells) was associated with disease severity but not with long-term symptoms (47). Moreover, Blankenburg et al (48) reported no significant differences between the symptoms of the SARS-CoV-2-seropositive and seronegative children, suggesting that most of the symptoms are due to lockdown syndrome rather than viral infection.…”