The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos

被引:31
作者
Via, M. [1 ]
De Giacomo, A.
Corvol, H.
Eng, C.
Seibold, M. A.
Gillett, C.
Galanter, J.
Sen, S.
Tcheurekdjian, H. [2 ]
Chapela, R. [3 ]
Rodriguez-Santana, J. R.
Rodriguez-Cintron, W. [4 ]
Thyne, S. [5 ]
Avila, P. C. [6 ]
Choudhry, S. [7 ]
Burchard, E. Gonzalez [7 ]
机构
[1] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA
[2] Case Western Reserve Univ, Cleveland, OH 44106 USA
[3] Inst Nacl Enfermedades Respiratorias, Mexico City, DF, Mexico
[4] Vet Caribbean Hlth Care Syst, San Juan, PR USA
[5] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA
[6] Northwestern Univ, Div Allergy Immunol, Chicago, IL 60611 USA
[7] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
association study; asthma; latino populations; leukotriene; 5-LIPOXYGENASE; ASSOCIATION; POLYMORPHISMS; MONTELUKAST; MECHANISMS; ETHNICITY; HYDROLASE; PATHWAY;
D O I
10.1111/j.1365-2222.2009.03438.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
P>Background 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. Objective To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. Methods 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. Results 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). Conclusion Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.
引用
收藏
页码:582 / 589
页数:8
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