Polymorphism of OLR1 Gene Encoding Oxidized LDL Receptor LOX-1 Modifies the Course of Necrotizing Pulmonary Infection

Necrotizing pulmonary infections (NPI) emerge as severe complications of community-acquired pneumonia (CAP), and immune system cells are involved in their pathogenesis. Highly informative biomarkers are required to determine high-risk patients to prevent life-threatening complications of NPI. Previously, we have shown that variations in immune cell numbers can be employed as prognostic biomarkers in NPI. We proposed that genetic variants encoding receptors detected on the surface of neutrophils, monocytes, and macrophages migrating to lung tissues during inflammation may predict the unfavorable course of NPI. One of these candidate genes could be the OLR1 gene, which encodes LOX-1 receptors that bind oxidized low-density lipoproteins oxLDL on the surface of immune and other cells.

The aim of the study. To find out the OLR1 gene single nucleotide polymorphism contribution to the clinical course of NPIs (pleural empyema) and variability in the number of immune cells in patients with post-CAP NPI.

Materials and methods. The study included patients of the Moscow City Hospital (aged 18–87 years, n = 216) with NPIs developed after CAP. Categorical data were described by indicating absolute values, which were compared using four-field contingency tables and the χ² test with Yates' correction for sample continuity and Fisher's exact test (FET).

Results. NPIs were the most common complication of CAP. In patients with NPI and the minor allele G OLR1 rs11053646, which encodes the LOX-1 167N variant, the course of the disease was less likely to be complicated by a fistula (p = 0.0015; exact Fisher test (EFT); OR = 3.55, 95% CI: 1.55–8.13; RR = 2.37, 95% CI: 1.24–4.50; n = 216). However, the significance of this association was influenced by previous COVID-19 documented in patient's medical history based on PCR test results. For patients who had been infected with COVID-19, this association persisted (p = 0.0058; EFT; OR = 7.27, 95% CI: 1.54–34.3; RR = 4.28, 95% CI:1.31–16.23; n = 81), whereas in patients with no PCR test confirmed COVID-19, this association was not statistically significant (p = 0.1065, EFT, n = 135). Thus, only post-COVID-10 carriers of the minor allele G OLR1 rs11053646 were protected from a severe course of NPIs complicated with fistula development. A study in a limited subgroup of patients showed a trend for a fistula development to associate with increased OxLDL plasma concentration of more than 100 ng/ml (p = 0.045; n = 19).

Conclusion. Post-COVID-19 сarriers of major OLR1 rs11053646 CC genotype exhibit increased risk for the unfavorable course of NPI (pleural empyema) complicated with fistula. The presence of alternative G allele of OLR1 rs11053646 in patient genotype associates with favorable course of NPIs.

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