Association of FCER1A genetic polymorphisms with risk for chronic spontaneous urticaria and efficacy of nonsedating H1-antihistamines in Chinese patients

Abstract

Antihistamines are the first-line treatment for chronic urticaria (CU). However, some CU patients are relatively refractory to antihistamines. The mechanism underlying the interindividual variation is still unknown. The α-chain of the high-affinity IgE receptor is crucial to the IgE-mediated allergic response. The present study is to investigate whether FCER1A polymorphisms are associated with the risk of CSU, and to determine whether these polymorphisms influence the therapeutic efficacy of nonsedating H1-antihistamines. 191 CSU patients treated by nonsedating H1-antihistamines monotherapy (including desloratadine, mizolastine or fexofenadine) were prospectively enrolled in this study. The response to antihistamines monotherapy was assessed by urticaria activity score (UAS7) after 4 weeks of treatment. FCER1A rs2298805, rs10908703 and rs2494262 genotypes were determined by Sequenom Mass Array technology or direct sequencing. There was significant difference in the allele frequency of rs2298805A between CSU patients and 177 healthy subjects (5.3 vs 10.2 %, P = 0.012, OR = 0.491, 95 % CI 0.278-0.865), and also significant difference in the allele frequency of rs2298805A between effective and ineffective groups (7.5 vs 1.0 %, P = 0.015, OR = 8.328, 95 %CI 1.1-63.039). In addition, rs2298805 polymorphism was significantly associated with total serum IgE concentrations (P = 0.011). There were no differences in the rs10908703 and rs2494262 either between CSU patients and healthy controls, or between effective and ineffective groups. These data suggest that rs2298805 might be associated with risk for CSU and the therapeutic efficacy of nonsedating H1-antihistamines in Chinese patients with CSU.

C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

“…Additionally, our previous studies have determined the genetic polymorphisms that are associated with the risks of CSU susceptibility. For instance, FCER1A rs2298805G, ORAI1 rs3741596A and rs12313209T increased the risks to CSU susceptibility . CRP acted as an acute phase protein in inflammation .…”

“…All the patients were treated with non‐sedating H1 antihistamine monotherapy. The inclusion and exclusion criteria for enrolment were the same as in our previous studies . This study was approved by the Ethics Committee of Xiangya Hospital and was registered on the Chinese Clinical Trial Registry online (the registration number is ChiCTR‐OCH‐14004518).…”

“…The efficacy of the antihistamines was evaluated using the weekly urticaria activity score (UAS7) by two professional dermatologists independently, both at baseline and after antihistamine monotherapy for 4 weeks. Responders were defined as those patients who had an improvement in UAS7 scores above 50% after the 4‐week treatment …”

FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS

“…Additional clinical associations for FCER1A SNPs are the putative association of the SNP rs2298804 with the risk of developing systemic lupus erythematosus in a study carried out in China (Yang et al, 2013 ), and the association of the SNP rs2298805 with the risk of developing chronic spontaneous urticaria in Chinese individuals (Guo et al, 2015 ). These SNPs are ethnic-specific as they have only been identified in Oriental individuals, but they do not occur in Caucasian individuals according to the 1000 genomes website.…”

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

“…One of the most widely studied functional SNPs in ABCB1 gene is C3435T (rs1045642, ILe 1145ILe) in exon 26 [25], which also has a higher frequency in Chinese population than that in other ethnic groups including Caucasian and African populations [26][27][28]. Other research groups have reported of a correlation between genetic polymorphisms of allergic response proteins, such as IgE receptor (FCERIA) and component 5a receptor 1 (C5AR1), and the therapeutic efficacy or side effects of mizolastine in vivo [29][30][31]. But whether genetic variants of UGT1A1, CYP3A5 and ABCB1 are associated with pharmacokinetic interindividual variation of mizolastine and whether these variant genotypes influence the metabolic phenotypes of mizolastine is still unknown.…”