Influence of component 5a receptor 1 (C5AR1) -1330T/G polymorphism on nonsedating H1-antihistamines therapy in Chinese patients with chronic spontaneous urticaria

J Dermatol Sci. 2014 Dec;76(3):240-5. doi: 10.1016/j.jdermsci.2014.09.012. Epub 2014 Oct 8.

Abstract

Background: The nonsedating H1-antihistamines are the first-line medicines for chronic spontaneous urticaria (CSU) patients. However, not all these patients respond well to the antihistamines, and the mechanisms underlying the interindividual differences are still unclear. C5AR1 gene encodes the component 5a receptor (C5aR) protein, which has been reported to play an important role in chronic spontaneous urticaria.

Objective: This study aimed to investigate whether the single nucleotide polymorphisms (SNPs) in C5AR1 are associated with CSU susceptibility and antihistamines therapeutic efficacy in Chinese CSU patients.

Methods: A total of 191 CSU patients and 102 healthy controls were prospectively studied in our study. CSU patients were treated by nonsedating H1-antihistamines monotherapy for 4 weeks. The C5AR1 -1330T/G (rs11673309) genotype was determined by Sequenom Massarray.

Results: Among these 191 CSU patients, there were 114 patients who were treated with desloratadine, 65 were treated with mizolastine, and 12 with fexofenadine. The-1330T alleles in CSU patients were significantly higher than controls (0.555 vs. 0.466, P=0.040, OR=1.429 [1.016-2.010]). The poorest response to desloratadine was observed in heterozygotes, when compared with either GG or TT homozgote (P=0.001). However, there was no significant difference in three genotypes when treated with mizolastine group (P=0.215).

Conclusion: We concluded that the C5AR1 SNP -1330T/G may serve as a useful pharmacodynamic predictor of nonsedating H1-antihistamines efficacy in CSU patients, and -1330T alleles may be taken as a risk factor for the CSU.

Keywords: Antihistamines; C5AR1 polymorphism; Chronic spontaneous urticaria; Desloratadine; Mizolastine; UAS7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian People / genetics
  • Benzimidazoles / therapeutic use
  • Case-Control Studies
  • China
  • Chronic Disease
  • Female
  • Histamine H1 Antagonists, Non-Sedating / therapeutic use*
  • Humans
  • Loratadine / analogs & derivatives
  • Loratadine / therapeutic use
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Receptor, Anaphylatoxin C5a / genetics*
  • Risk Factors
  • Treatment Outcome
  • Urticaria / drug therapy*
  • Urticaria / genetics*
  • Urticaria / immunology
  • Young Adult

Substances

  • Benzimidazoles
  • C5AR1 protein, human
  • Histamine H1 Antagonists, Non-Sedating
  • Receptor, Anaphylatoxin C5a
  • mizolastine
  • Loratadine
  • desloratadine