Asthma and allergic rhinitis associate with the rs2229542 variant that induces a p.Lys90Glu mutation and compromises AKR1B1 protein levels.

Asthma and rhinitis are two of the main clinical manifestations of allergy, in which increased reactive oxygen or electrophilic species can play a pathogenic role. Aldose reductase (AKR1B1) is involved in aldehyde detoxification and redox balance. Recent evidence from animal models points to a role of AKR1B1 in asthma and rhinitis, but its involvement in human allergy has not been addressed. Here, the putative association of allergic rhinitis and asthma with AKR1B1 variants has been explored by analysis of single-strand variants on the AKR1B1 gene sequence in 526 healthy subjects and 515 patients with allergic rhinitis, 366 of whom also had asthma. We found that the rs2229542 variant, introducing the p.Lys90Glu mutation, was significantly more frequent in allergic patients than in healthy subjects. Additionally, in cells transfected with expression vectors carrying the wild-type or the p.Lys90Glu variant of AKR1B1, the mutant consistently attained lower protein levels than the wild-type and showed a compromised thermal stability. Taken together, our results show that the rs2229542 variant associates with asthma and rhinitis, and hampers AKR1B1 protein levels and stability. This unveils a connection between the genetic variability of aldose reductase and allergic processes.

A Nonsynonymous FCER1B SNP is Associated with Risk of Developing Allergic Rhinitis and with IgE Levels.

Allergic rhinitis is associated with elevated serum IgE levels. IgE response is mediated by the high-affinity IgE receptor (FcεRI), which is polymorphic. Studies analyzing the association between allergic rhinitis and FcεRI variants have been conducted with controversial results. The objective of this study is to analyze, in 1,041 individuals, the putative clinical association of allergic rhinitis with common polymorphisms in FcεRI subunits genes. These SNPs included FECR1A rs2494262, rs2427837 and rs2251746; FECR1B rs1441586, rs569108 and rs512555; FCER1G rs11587213, rs2070901 and rs11421. Statistically significant differences were observed for the FCER1B rs569108 and rs512555 polymorphisms frequencies when comparing patients with allergic rhinitis without asthma and controls. The OR (95% CI) value for the 237Gly allele (rs569108) is equal to 0.26 (0.08-0.86, P = 0.017) and for the G allele (rs512555) it is equal to 0.27 (0.08-0.88, P = 0.020). These two SNPs are linked (D' = 1.0, LOD = 56.05). Also observed was a statistically significant trend towards lower IgE values among allergic rhinitis patients with variant alleles for both SNPs. In conclusion, in patients with allergic rhinitis without asthma, the FCER1B rs569108 and rs512555 polymorphisms are associated with increased risk of developing allergic rhinitis and with lower IgE levels.