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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, Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability, Human Molecular Genetics, Volume 13, Issue 21, 1 November 2004, Pages 2691–2697, https://doi.org/10.1093/hmg/ddh279
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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.
