Lung Biology Center, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Clin Exp Allergy. 2010 Apr;40(4):582-9. doi: 10.1111/j.1365-2222.2009.03438.x. Epub 2010 Jan 11.
Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive.
To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans.
The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin.
In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample).
Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.
白三烯在过敏和炎症性疾病中发挥重要作用，但关于花生四烯酸 5-脂氧合酶激活蛋白（ALOX5AP）和白三烯 A（4）水解酶（LTA4H）在哮喘中的作用的报道尚无定论。
确定 ALOX5AP 和 LTA4H 基因中的多态性是否是两个不同拉丁裔群体（墨西哥裔和波多黎各裔）中哮喘的危险因素。
对两组个体进行 LTA4H 基因测序，以确定新的多态性。分析 ALOX5AP 和 LTA4H 基因中的单核苷酸多态性（SNP）与来自墨西哥和波多黎各的 687 个亲子三系中的哮喘和哮喘相关表型的关联。
在 LTA4H 中，发现了五个以前未知的多态性。LTA4H 内的两个 SNP（rs17525488 和 rs2540493）对拉丁裔人群的哮喘有保护作用（分别为 P=0.007 和 0.05）。在墨西哥患者中，LTA4H 多态性与基线肺功能和 IgE 水平相关。对于 ALOX5AP，SNP rs10507391 的次要等位基因与哮喘（比值比=0.78，P=0.02）和波多黎各人群的基线肺功能（P=0.018）的保护作用相关。在 LTA4H（rs17525488）和 ALOX5AP（rs10507391）之间鉴定到基因-基因相互作用，（P=0.003，在合并样本中）。
我们的结果支持 LTA4H 和 ALOX5AP 变体作为拉丁裔人群哮喘危险因素的作用。
