title: Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and aspirin exacerbated respiratory diseases.
abstract: Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in the FPR2 and AERD. Asthmatics were categorized into AERD <15% decreases in forced expiratory volume in one second (FEV(1)), and/or naso-ocular reactions after oral aspirin challenge (n=170) and aspirin-tolerant asthma (ATA, n=268). In all, 11 SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in peripheral blood were measured using flow cytometric analysis. We performed RT-PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic regression analysis showed that the minor allele frequency of FPR2 -4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268) (P=0.006, P(corr)=0.04, recessive model). The decline of FEV(1) after aspirin challenge was significantly lower in the subjects with GG homozygotes of FPR2 -4209T>G than those with the other genotypes (P=0.0002). Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G may have a protective role against the development of AERD, via increase of FPR2 protein expression in inflammatory cells.
authors.affiliation: Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Wonmi-gu, Bucheon, Republic of Korea.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Tae-Hyeong
authors.initials: TH
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyoung-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D055963:Asthma, Aspirin-Induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume / Q000187:drug effects; D015870:Gene Expression; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D007438:Introns; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics* / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000235:genetics* / Q000378:metabolism; D014797:Vital Capacity; D055815:Young Adult
chemical_list: C105101:FPR2 protein, human; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D001241:Aspirin