Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability

Jing Long Huang, Pei Song Gao, Rasika A. Mathias, Tsung Chieh Yao, Li Chen Chen, Ming Ling Kuo, Shih Chang Hsu, Beverly Plunkett, Alkis Togias, Kathleen C. Barnes, Cristiana Stellato, Terri H. Beaty, Shau Ku Huang

Research output: Contribution to journalArticle

Abstract

The gene, CRTH2, encoding a receptor for prostaglandin D2 (PGD2), is located within the peak linkage region for asthma on chromosome (Chr) 11q reported in African American families. Family-based analysis of asthma and two common SNPs [G1544C and G1651A (rs545659)] in the 3′-untranslated region of CRTH2 showed significant evidence of linkage in the presence of disequilibrium for the 1651G allele (P = 0.003) of SNP rs545659. Haplotype analysis yielded additional evidence of linkage disequilibrium for the 1544G-1651G haplotype (P < 0.001). Population-based case-control analyses were conducted in two independent populations, and demonstrated significant association of the 1544G-1651G haplotype with asthma in an African American population (P = 0.004), and in a population of Chinese children (P < 0.001). Moreover, in the Chinese children the frequency of the 1651G allele in near-fatal asthmatics was significantly higher than mild-to-moderate asthmatics (P = 0.001) and normal controls (P < 0.001). The 1651G allele of SNP re545659 was also associated with a higher degree of bronchial hyperresponsiveness (P < 0.027). Transcriptional pulsing experiments showed that the 1544G-1651G haplotype confers a significantly higher level of reporter mRNA stability, when compared with a non-transmitted haplotype (1544C-1651A), suggesting that the CRTH2 gene on Chr. 11q is a strong candidate gene for asthma.

Original languageEnglish (US)
Pages (from-to)2691-2697
Number of pages7
JournalHuman molecular genetics
Volume13
Issue number21
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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