Association of CRTH2 gene polymorphisms with the required dose of antihistamines in patients with chronic urticaria.
BACKGROUND
Chronic urticaria (CU), defined as the recurring incidence of wheals with or without angioedema for more than 6 weeks, is a common disorder associated with mast cell activation, degranulation, and histamine release. Considering the association between the CRTH2 gene and mast cells, we investigated the association of this gene polymorphism with the CU phenotype and antihistamine drug requirement in patients with CU.


METHODS
Two groups consisting of 384 patients with CU and 231 patients as normal controls (NCs) were enrolled from the Department of Allergy and Rheumatology, Ajou University Hospital, Suwon, Korea. Two polymorphisms of the CRTH2 gene, -466T>C and -129C>A were genotyped using primer extension methods.


RESULTS
No significant differences were detected in the genotype and allele frequencies of the two CRTH2 polymorphisms between the CU and NC groups, and no significant associations were observed with clinical parameters, such as atopy status, serum total IgE, prevalence of autoantibodies and duration of CU. However, CU patients with homozygous TT genotypes had significantly higher dose requirements of antihistamines to control the CU symptoms (164.56 +/- 115.62 vs 137.38 +/- 90.15 loratadine equivalents, mg/week) than those with the CT and CC genotypes (p = 0.025). The luciferase activity was significantly enhanced in the construct containing CRTH2 466C compared with the -466T-containing construct (p < 0.001). Co-transfection experiments with GATA-3 (300 ng) and the -466T and -466C CRTH2 alleles revealed that the CRTH2 -466T allele produced a greater increase in induction of luciferase activity than the -466C allele (p < 0.001).


CONCLUSIONS
The CRTH2 -466T>C gene polymorphism may not affect on the phenotype of CU, but contributes to the required dose of antihistamines in patients with CU.
Palikhe
Nami Shrestha
NS
Department of Allergy and Rheumatology, Ajou University School of Medicine, Youngtonggu Wonchon Dong San 5, Suwon, Korea.
Kim
Seung-Hyun
SH
Ye
Young-Min
YM
Hur
Gyu-Young
GY
Cho
Bo-Young
BY
Park
Hae-Sim
HS
D002460:Cell Line; D002908:Chronic Disease; D017931:DNA Primers; D050990:GATA3 Transcription Factor / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008407:Mast Cells / Q000502:physiology; D010641:Phenotype; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D012016:Reference Values; D014162:Transfection; D014581:Urticaria / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
D017931:DNA Primers; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D006633:Histamine Antagonists; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D007073:Immunoglobulin E; C036293:prostaglandin D2 receptor