Copy Number Variation in Asthma: An Integrative Review

Abstract

Asthma is a complex disease with varied clinical manifestations resulting from the interaction between environmental and genetic factors. While chronic airway inflammation and hyperresponsiveness are central features, the etiology of asthma is multifaceted, leading to a diversity of phenotypes and endotypes. Although most research into the genetics of asthma focused on the analysis of single nucleotide polymorphisms (SNPs), studies highlight the importance of structural variations, such as copy number variations (CNVs), in the inheritance of complex characteristics, but their role has not yet been fully elucidated in asthma. In this context, an integrative review was conducted to identify the genes and pathways involved, the location, size, and classes of CNVs, as well as their contribution to asthma risk, severity, control, and response to treatment. As a result of the review, 16 articles were analyzed, from different types of observational studies, such as case-control, cohort studies and genotyped-proband or trios design, that have been carried out in populations from different countries, ethnicities, and ages. Chromosomes 12 and 17 were the most studied in three publications each. CNVs located on 12 chromosomes were associated with asthma, the majority being found on chromosome 6p and 17q, of the deletion type, encompassing 30 different coding-protein genes and one pseudogene region. Six genes with CNVs were identified as significant expression quantitative locus (eQTLs) with mean expression in asthma-related tissues, such as the lung and whole blood. The phenotypic variability of asthma may hinder the clinical application of these findings, but the research shows the importance of investigating these genetic variations as possible biomarkers in asthma patients.

Keywords: Biological/genetic markers; Deletions; EQTL; Insertions; Phenotypes of asthma; Phenotypic variability; Precision medicine; Structural variants.