title: Association analysis of RGS7BP gene polymorphisms with aspirin intolerance in asthmatic patients.
abstract: BACKGROUND
  Signal-regulated palmitoylation of RGS7BP(regulator of G-protein-signaling 7-binding protein) initiates the activation of G-protein-coupled receptors (GPCRs), including muscarinic receptors, which contribute to the development of asthma and its subphenotypes.
  
  
  OBJECTIVE
  To determine the association of RGS7BP gene polymorphisms with the development of aspirin-exacerbated respiratory disease (AERD).
  
  
  METHODS
  We evaluated the association of RGS7BP gene polymorphisms with response to oral aspirin challenge and with responsiveness to methacholine challenge. RGS7BP messenger RNA splice variants in peripheral blood platelets from patients with different single-nucleotide polymorphisms were analyzed by reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Logistic regression analysis of RGS7BP gene polymorphisms in patients with AERD (n = 102) and aspirin-tolerant asthma (n = 429) revealed that a haplotype of block 3 consisting of rare alleles +98092 C>G, +98853 C>T, and +104450 T>G of the RGS7BP gene was associated with AERD. Multiple linear regression analysis showed that asthmatic patients carrying ht2/ht2 in block 3 were more responsive to aspirin challenge than those not carrying ht2 (P = .008 in a codominant model). The log-transformed provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% for methacholine was significantly dependent on the BL3-ht2 haplotype. No significant differences in platelet expression of different RGS7BP messenger RNA splice variants were detected between those with and without the BL3-ht2 haplotype.
  
  
  CONCLUSIONS
  BL3-ht2 of RGS7BP may be an important genetic variant associated with AERD. The haplotype of block 3 may play a protective role against aspirin hypersensitivity in asthma, perhaps by altering the responsiveness of muscarinic receptors.
authors: Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea.
authors: Eun Hee
authors: EH
authors: Lee
authors: Byung Lae
authors: BL
authors: Park
authors: Se-Min
authors: SM
authors: Park
authors: Shin Hwa
authors: SH
authors: Lee
authors: Sung-Woo
authors: SW
authors: Park
authors: Jong-Sook
authors: JS
authors: Park
authors: Soo-Taek
authors: ST
authors: Uh
authors: Mi-Kyeong
authors: MK
authors: Kim
authors: Inseon S
authors: IS
authors: Choi
authors: Sang Heon
authors: SH
authors: Cho
authors: Chein-Soo
authors: CS
authors: Hong
authors: Jae-Young
authors: JY
authors: Lee
authors: Byoung Whui
authors: BW
authors: Choi
authors: Hyoung Doo
authors: HD
authors: Shin
authors: Choon-Sik
authors: CS
authors: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins; D012313:RNA / Q000737:chemistry / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020710:RGS Proteins; C542323:RGS7BP protein, human; D043562:Receptors, G-Protein-Coupled; D012313:RNA; D001241:Aspirin