Objective: Cysteinyl leukotriene receptor 2 (CYSLTR2) is one of the receptors for the cysteinyl leukotrienes (CYSLTs), which cause bronchoconstrictions, vascular hyperpermeability and mucus hypersecretion in asthmatic patients. CYSLTR1 antagonists have been shown to be effective in the treatment of chronic asthma. CYSLTR2 is located approximately 300 kb from D13S153, which is reportedly linked to asthma in several populations. We characterized the genomic structure of humans CYSLTR2, determined the putative major promoter region and conducted association studies pertaining to polymorphisms in CYSLTR2 and asthma.
Methods And Results: We identified three novel exons in the 5' untranslated region of CYSLTR2 by rapid amplification of cDNA ends and identified eight novel polymorphisms in CYSLTR2 by direct sequencing. A transmission disequilibrium test with 137 Japanese asthmatic families revealed that the -1220A > C polymorphism is associated with the development of asthma (P = 0.0066). In addition, a polymorphism in the putative promoter region caused different promoter activities in vitro.
Conclusion: Our results suggest that CYSLTR2 is one of the genes that contributes to susceptibility to asthma in the Japanese population.
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