Division of Therapeutics and Molecular Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
BMC Med Genet. 2012 Nov 20;13:110. doi: 10.1186/1471-2350-13-110.
Polymorphisms spanning genes involved in the production of leukotriene B4 (LTB4) e.g. ALOX5AP and LTA4H are associated with asthma susceptibility, suggesting a role for LTB4 in disease. The contribution of LTB4receptor polymorphism is currently unknown. The aim of this study was to characterise the genes for the two pivotal LTB4 receptors, LTB4R1 and LTB4R2 in lung tissue and determine if polymorphisms spanning these genes are associated with asthma and disease severity.
Rapid amplification of cDNA ends (RACE) was used to characterise the LTB4R1 and LTB4R2 gene structure in lung. The LTB4R1/2 locus on chromosome 14q11.2 was screened for polymorphic variation. Six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in 370 Caucasian asthma families and 299 Adult Asthma Individuals (n=1877 total) and were evaluated for association with asthma and severity (BTS) outcome measures using Family Based Association Test, linear regression and chi square.
LTB4R1 has complex mRNA arrangement including multiple 5'-untranslated exons, suggesting additional levels of regulation. Three potential promoter regions across the LTB4R1/2 locus were identified with some airway cell specificity. 22 SNPs (MAF>0.01) were validated across the LTB4R locus in the Caucasian population. LTB4R1 and LTB4R2 SNPs were not associated with asthma susceptibility, FEV1 or severity.
LTB4R1 and LTB4R2 shows splice variation in the 5'-untranslated region and multiple promoter regions. The functional significance of this is yet to be determined. Both receptor genes were shown to be polymorphic. LTB4R polymorphisms do not appear to be susceptibility markers for the development of asthma in Caucasian subjects.
涉及白三烯 B4 (LTB4)产生的基因（如 ALOX5AP 和 LTA4H）的多态性与哮喘易感性相关，表明 LTB4 在疾病中起作用。LTB4 受体多态性的贡献目前尚不清楚。本研究的目的是研究肺组织中两个关键的 LTB4 受体 LTB4R1 和 LTB4R2 的基因结构，并确定跨越这些基因的多态性是否与哮喘和疾病严重程度相关。
采用快速扩增 cDNA 末端 (RACE) 技术对 LTB4R1 和 LTB4R2 基因结构进行了特征分析。在染色体 14q11.2 上筛选 LTB4R1/2 基因座的多态性变化。在 370 个白种人哮喘家族和 299 个成人哮喘个体（共 1877 例）中对 6 个 LTB4R 单核苷酸多态性 (SNP) 进行了基因分型，并使用基于家庭的关联测试、线性回归和卡方检验评估它们与哮喘和严重程度 (BTS) 结局指标的相关性。
LTB4R1 的 mRNA 排列复杂，包括多个 5'-非翻译外显子，提示存在额外的调节水平。在 LTB4R1/2 基因座上鉴定出三个潜在的启动子区域，具有一定的气道细胞特异性。在白种人群中，LTB4R 基因座上有 22 个 SNP（MAF>0.01）得到验证。LTB4R1 和 LTB4R2 SNP 与哮喘易感性、FEV1 或严重程度无关。
LTB4R1 和 LTB4R2 在 5'-非翻译区和多个启动子区域存在剪接变异。其功能意义尚待确定。两个受体基因均表现出多态性。LTB4R 多态性似乎不是白种人群哮喘发病的易感性标志物。
