染色体13q14上半胱氨酸白三烯受体2多态性与特应性哮喘的关系。

Hiromi Fukai, Yoshino Ogasawara, Ohsuke Migita, Minori Koga, Kunio Ichikawa, Masanao Shibasaki, Tadao Arinami, Emiko Noguchi
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引用次数: 38

摘要

目的:半胱氨酸白三烯受体2 (CYSLTR2)是引起哮喘患者支气管收缩、血管高通透性和粘液高分泌的半胱氨酸白三烯受体之一。CYSLTR1拮抗剂已被证明对慢性哮喘的治疗有效。CYSLTR2位于距离D13S153约300 kb的位置,据报道,D13S153与几个人群的哮喘有关。我们描述了人类CYSLTR2的基因组结构,确定了假定的主要启动子区域,并进行了CYSLTR2多态性与哮喘的关联研究。方法与结果:通过cDNA末端的快速扩增,在CYSLTR2的5'非翻译区鉴定出3个新的外显子;通过直接测序,鉴定出8个新的CYSLTR2多态性。通过对137个日本哮喘家族的遗传不平衡检验,发现-1220A > C多态性与哮喘的发生有关(P = 0.0066)。此外,假设启动子区域的多态性在体外引起不同的启动子活性。结论:本研究结果提示CYSLTR2是导致日本人群哮喘易感性的基因之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma.

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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