Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.
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.
Kim
Sang-Heon
SH
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Kim
Yoon-Keun
YK
Park
Heung-Woo
HW
Jee
Young-Koo
YK
Kim
Sang-Hoon
SH
Bahn
Joon-Woo
JW
Chang
Yoon-Seok
YS
Kim
Seung-Hyun
SH
Ye
Young-Min
YM
Shin
Eun-Soon
ES
Lee
Jong-Eun
JE
Park
Hae-Sim
HS
Min
Kyung-Up
KU
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*
D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D001241:Aspirin