title: Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.
abstract: BACKGROUND
  Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype.
  
  
  METHODS
  We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls).
  
  
  RESULTS
  Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015).
  
  
  CONCLUSIONS
  These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Joon-Woo
authors.initials: JW
authors.lastname: Bahn
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
mesh_terms: D000328:Adult; D000483:Alleles; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004361:Drug Tolerance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011453:Prostaglandins / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics*
chemical_list: D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D001241:Aspirin