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

Abstract

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.

• Authors: 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
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 13 Issue 21 Pg. 2691-7 (Nov 01 2004) ISSN: 0964-6906 [Print] England
• PMID: 15345705 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 3' Untranslated Regions
• RNA, Messenger
• Receptors, Immunologic
• Receptors, Prostaglandin
• Immunoglobulin E
• prostaglandin D2 receptor

Topics

• 3' Untranslated Regions
• Black or African American (ethnology, genetics)
• Alleles
• Animals
• Asian People
• Asthma (ethnology, genetics)
• Case-Control Studies
• Child
• Child, Preschool
• Chromosomes, Human, Pair 11
• Female
• Genetic Linkage
• Genetic Variation
• Genetics, Population
• Haplotypes
• Humans
• Immunoglobulin E (blood)
• Linkage Disequilibrium
• Male
• Mice
• NIH 3T3 Cells
• Polymorphism, Single-Stranded Conformational
• RNA, Messenger (metabolism)
• Receptors, Immunologic (genetics)
• Receptors, Prostaglandin (genetics)
• Risk Factors
• Sequence Analysis, DNA
• Th2 Cells (metabolism)