Relationship Between Allergic Reaction To Penicillins And Genetic Polymorphisms Of IL-4Rα And STAT6

Penicillins are widely used in clinical practice with the highest prevalence of allergic response among numerous medicines, in which some serious response can cause allergic shock or even death. Similar to other allergic disorders, the value of total serum IgE or specific IgE will be elevated following the occurrence of penicillins allergic response. By far, IL-4 is the highest regulator for IgE. The biologic effects of IL-4 are released through the adhesion of IL-4R on target cell surface and the activation of relating signal transduction pathways. This experiment is sought to study the IL-4Ra gene and the STAT6 gene in the IL-4R signal transduction pathway, and to explore the relationship of genetic polymorphisms with specific serum IgE and with allergic reaction of penicillins.Methods1. Radioallergosorbent test (RAST)In total 242 patients with allergic reaction to penicillins and 86 healthy subjects, eight categories of specific immunoglobulin E (IgE) of penicillins (BPO-PLL, PVO-PLL, APO-PLL, AXO-PLL, BPA-PLL, PVA-PLL, APA-PLL, AXA-PLL) were detected with RAST.2. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)Polymorphisms of IL-4RαQ576R, IL-4RαI75V and STAT6 in2SNP3 were genotyped by PCR-RFLP in 242 patients with allergic reaction to penicillins and 220 healthy subjects.Results1. Serum specific IgE levelIn 242 patients with allergic response, no significant difference of serum specific IgE level was found intra groups of positive and negative dermal test or intra groups with or without allergic history (59% vs 65%, 60% vs 61 %).2. Allergic reaction of penicilins and SNPs of related genes2.1 Hardy-Weinberg equilibrium testIn both allergic patients and healthy subjects, three genetic sites of IL-4Ra Q576R, IL-4Ra I75V and STAT6 in2SNP3 met Hardy-Weinberg equilibrium test.2.2 Association between penicillins allergy and IL-4Ra Q576RThe frequency of AA genotype in healthy subjects was 64% in the IL-4Ra Q576R, compared with it, which in allergic patients, especially in allergic patients of skin test positive, was significantly higher (76% vs 64%, 77% vs 64%, P<0.05). Similar results were observed between patients of major or minor antigenic determinant positive and healthy subjects (77% vs 64%, 81% vs 64%, P<0.05). The frequency of Q576R-AA genotype in the group of positive APO-IgE was significantly higher than that in healthy subjects (86% vs 64%, P<0.05).2.3 Association between penicillins allergy and IL-4RαI75VThere was no significant difference between allergic patients and healthy subjects in the IL-4Ra I75V.2.4 Association between penicillins allergy and STAT6 in2SNP3In the STAT6 in2SNP3, the frequency of CC genotype was 47% in healthy subjects, which was significantly higher in allergic patients compared with it (60% vs 47%, P<0.01). At the same time, the frequency of CC genotype in the group of allergic symptoms, especially of urticaria, was significantly higher than that in healthy subjects (65% vs 47%, 70% vs 47%, P<0.05), and that in the groups of positive BPO-and AXO-IgE was significantly higher than that in healthy subjects too (64% vs 47%, 66% vs 47%, P<0.05). While the frequency of CC genotype in the group of positive AXO-IgE was significantly higher than that in the group of negative AXO-IgE (66% vs 57%, P<.05).3. Linkage disequilibrium analysis of IL-4RαQ576R and I75VWith SHEsis software, no linkage disequilibrium was constructed between two genetic sites of IL-4RαQ576R and I75V.4. Allergic reaction to penicilins and haplotype of IL-4RαIn four haplotypes of IL-4Rαcomposed of two polymorphic genetic sites of Q576R and I75V, haplotype of Q576/I75 occurred frequently in allergic patients than that in controls (42% vs 35%, P<0.05).Conclusions1. Allergic reaction to penicillins associates with genetic polymorphisms of IL-4Ra Q576R and STAT6 in2SNP3.2. The polymorphism of IL-4RαQ576R is associated with positive result of skin test, the synthesis of APO-IgE and the symptom of urticaria.3. The polymorphism of STAT6 in2SNP3 is association with the synthesis of AXO-and BPA-IgE, all of the symptoms especially urticaria.4. IL-4Ra Q576/I75 haplotype is associated with allergic reaction to penicillins.