Genetic variants in insulin, leptin, and their receptors are associated with overweight in a Brazilian asthma cohort

Abstract

Obesity is often characterized by meta-inflammation and is influenced by the interaction between genetic predisposition and environmental factors. Common features include impaired insulin action and elevated leptin concentrations, which are accompanied by a simultaneous reduction in sensitivity to these hormones. We hypothesized that single nucleotide variants in protein-coding genes and their receptors may influence the dysfunctions observed in obesity. For that, we investigate the association between single nucleotide variants in the LEP, LEPR, INS, and INSR genes with excess weight in a Brazilian population drawn from an asthma cohort. The study included 703 individuals with excess weight and 333 controls (individuals without overweight) from ProAR foundation. Genotyping was conducted using a commercial Illumina Multi-Ethnic Global Array panel (MEGA, Illumina), which contains 1.5 million markers. Logistic regression was employed to identify associations with the overweight using PLINK 2.0. The analysis was adjusted for age, sex, corticosteroids, and the principal component 1 representing ethnicity to control for confounding factors due to population structure. Variants in the LEP and LEPR genes exhibited the strongest associations with the risk of overweight in our population, whereas the associations with INSR were predominantly negative. The lone variant in the INS gene did not demonstrate a significant association with the outcome. Finally, anthropometric indices showed associations with various genotypes, particularly in the receptor variants. Associations in the genes studied with overweight and the distribution of body fat potentially impacts metabolic dysfunctions, which should be further investigated in other studies.