Evaluation of Adipokine Status and Leptin Receptor Gene Polymorphism in Patients with Severe Asthma

TL;DR

This study explores how leptin, adiponectin, and a gene variant may influence severe asthma, finding a link between a specific gene variant and uncontrolled asthma.

Contribution

The study identifies a potential genetic risk factor (LEPR Gln223Arg A/A allele) for severe asthma.

Findings

The adiponectin/leptin ratio correlates inversely with inflammation markers and positively with lung function.

The A/A genotype of the LEPR Gln223Arg polymorphism is associated with increased risk of uncontrolled asthma.

Patients with uncontrolled asthma had a high prevalence of metabolic syndrome.

Abstract

Background: Severe and difficult-to-control asthma occurs in 3–10% of patients in developed countries. The aim of our study was to investigate the association of the prognostic role of leptin and adiponectin, as well as the leptin receptor gene polymorphism Gln223Arg, in patients with difficult-to-control and severe asthma. Methods: The present study included 200 patients with asthma hospitalized in the Department of Pulmonology between January 2018 and December 2021. In all patients, in addition to routine clinical investigations, adiponectin, leptin and their ratio were analyzed, as well as levels of pro-inflammatory cytokines (IL-6, IL-8 and TNF-alpha). External respiratory function was also assessed. LEPR Gln223Arg single-nucleotide polymorphisms were genotyped by real-time PCR method. Results: Patients were randomized into two groups, depending on the severity of asthma: an uncontrolled asthma group and a controlled asthma group, according to the GINA criteria. Among patients with uncontrolled asthma, 101 subjects (74.3%) had metabolic syndrome (p < 0.001). There was an inverse association of the adiponectin/leptin ratio with the eosinophil count (B = −0.305, p < 0.001), IL-6 (B = −0.026, p < 0.001), IL-8 (B = −0.062, p < 0.001) and TNF-alpha (B = −0.047, p < 0.001) and a direct correlation with the level of FEV1 (B = 0.121, p < 0.001) and FVC (B = 0.104, p < 0.001). A probable association of homozygous A/A allele with increased risk of uncontrolled asthma was shown (p = 0.007). Conclusions: Leptin receptor polymorphism with A/A genotype may be associated with a higher probability of developing severe and difficult-to-control asthma.

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