Research article summary (published 18 Oct 2009):

Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization.

Full Abstract

BACKGROUND: We previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of the CysLTR2 gene. METHODS: We measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics having ht1+/+ and ht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively. RESULTS: We found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics having ht2+/+ than in those having ht1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines from ht2+/+ asthmatics than those from ht1+/+ asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containing c.-819T than one containing c.-819G. The luciferase activity of the c.-819T type of CysLTR2 promoter was higher than that of the c.-819G type. EGFP expression was higher in the EGFP-c.2078T 3'-UTR fusion construct than in the c.2078C construct. CONCLUSION: The sequence variants of CysLTR2 may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.

Author information

Author/s: Shin, Jeong-Ah (JA); Chang, Hun Soo (HS); Park, Se-Min (SM); Jang, An-Soo (AS); Park, Sung Woo (SW); Park, Jong Sook (JS); Uh, Soo-Taek (ST); Il Lim, Gune (G); Rhim, Taiyoun (T); Kim, Mi-Kyeong (MK); Choi, Inseon S (IS); Chung, Il Yup (IY); Park, Byung Lae (BL); Shin, Hyoung Doo (HD); Park, Choon-Sik (CS);

Affiliation: Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-767, Korea. jamies01(-atsign-)empal.com

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: BMC medical genetics (BMC Med Genet), published in England. (Language: eng)

Reference: 2009-; vol 10 (issue ) : pp 106

Dates: Created 2009/10/29; Completed 2009/10/30; Revised 2009/10/30;

PMID: 19840403, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aspirin - adverse effects Asthma - chemically induced; genetics Cell Line Drug Hypersensitivity - genetics Electrophoretic Mobility Shift Assay Flow Cytometry Gene Expression Genetic Predisposition to Disease

Haplotypes Humans Luciferases Polymorphism, Single Nucleotide Promoter Regions, Genetic RNA Stability - genetics RNA, Messenger - biosynthesis Receptors, Leukotriene - genetics

Associated Chemicals: RNA, Messenger (0) ; Receptors, Leukotriene (0) ; cysteinyl leukotriene receptor 2 (0) ; Aspirin (50-78-2) ; Luciferases (EC 1.13.12.-)

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