Journal
HUMAN MOLECULAR GENETICS
Volume 13, Issue 21, Pages 2691-2697Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddh279
Keywords
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Funding
- NHLBI NIH HHS [HL-49612] Funding Source: Medline
- NIAID NIH HHS [AI-52468] Funding Source: Medline
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The gene, CRTH2, encoding a receptor for prostaglandin D-2 (PGD(2)), 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.
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