The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos |
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| Authors: | M Via A De Giacomo H Corvol C Eng M A Seibold C Gillett J Galanter S Sen H Tcheurekdjian R Chapela J R Rodríguez‐Santana W Rodríguez‐Cintrón S Thyne P C Avila S Choudhry E González Burchard |
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| Institution: | 1. Lung Biology Center, Department of Medicine;2. the Institute for Human Genetics;3. *Contributed equally to the work.;4. Department of Epidemiology & Biostatistics;5. Allergy/Immunology Associates Inc. and Case Western Reserve University, Cleveland, OH, USA;6. Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico;7. Centro de Neumología Pediátrica, CSP;8. Veterans Caribbean Health Care System, San Juan, Puerto Rico;9. Department of Pediatrics;10. Division of Allergy‐Immunology, Northwestern University, Chicago, IL, USA;11. Department of Biopharmaceutical Sciences, University of California, San Francisco, San Francisco, CA, USA |
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| Abstract: | 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 A4 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. Cite this as: M. Via, A. De Giacomo, H. Corvol, C. Eng, M. A. Seibold, C. Gillett, J. Galanter, S. Sen, H. Tcheurekdjian, R. Chapela, J. R. Rodríguez‐Santana, W. Rodríguez‐Cintrón, S. Thyne, P. C. Avila, S. Choudhry and E. González Burchard on behalf of the Genetics of Asthma in Latino Americans (GALA) Study, Clinical & Experimental Allergy, 2010 (40) 582–589. |
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| Keywords: | association study asthma latino populations leukotriene |
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