C5 and SRGAP3 Polymorphisms Are Linked to Paediatric Allergic Asthma in the Italian Population

Abstract

Asthma is a complex and heterogeneous disease, caused by the interaction between genetic and environmental factors with a predominant allergic background in children. The role of specific genes in asthmatic bronchial reactivity is still not clear, probably because of the many common pathways shared with other allergic disorders. This study is focused on 11 SNPs possibly related to asthma that were previously identified in a GWAS study. The genetic variability of these SNPs has been analysed in a population of 773 Italian healthy controls, and the presence of an association between the polymorphisms and the asthma onset was evaluated performing genotyping analysis on 108 children affected with asthma compared with the controls. Moreover, a pool of 171 patients with only allergic rhinoconjunctivitis has been included in the case–control analysis. The comparison of allele frequencies in asthmatic patients versus healthy controls identified two SNPs—rs1162394 (p = 0.019) and rs25681 (p = 0.044)—associated with the asthmatic condition, which were not differentially distributed in the rhinoconjunctivitis group. The rs25681 SNP, together with three other SNPs, also resulted in not being homogenously distributed in the Italian population. The significantly higher frequency of the rs25681 and rs1162394 SNPs (located, respectively, in the C5 and SRGAP3 genes) in the asthmatic population suggests an involvement of these genes in the asthmatic context, playing a role in increasing the inflammatory condition that may influence asthma onset and clinical course.

Association between lipid-lowering drugs and allergic diseases: A Mendelian randomization study

“…It is well known that asthma comprises multiple phenotypes, including allergic and nonallergic asthma, childhood and adult asthma, and obesity-related manifestations, with differences in presentation, pathogenesis, and course of the disease among different subtypes. 38 Additionally, variations in the pleiotropic effects of PCSK9 inhibitors across different disease contexts may contribute to divergent findings. Further research exploring these potential mechanisms and conducting meta-analyses to synthesize evidence from multiple studies could provide a more comprehensive understanding of the complex relationship between PCSK9 inhibitors and asthma risk.…”

Complement‐mediated immune mechanisms in allergy

“…However, reports that link such deficiencies or deletions to allergic diseases are limited. Originally identified as a gene locus that protects from the development of experimental allergic asthma in mice [11], C5 polymorphisms were recently linked to pediatric asthma in a cohort involving Italian pediatric asthmatic patients [25]. Also, genetic variations in C5, C3, and C3aR have been described in Japanese asthmatic patients that affect susceptibility to allergic asthma [26,27].…”