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. 2010 Apr;40(4):582-9.
doi: 10.1111/j.1365-2222.2009.03438.x. Epub 2010 Jan 11.

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

M Via  1 , 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; Genetics of Asthma in Latino Americans (GALA) Study
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The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos

M Via et al. Clin Exp Allergy. 2010 Apr.

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 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.

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Figures

Figure 1
Figure 1
Schematic diagrams of LTA4H and ALOX5AP genes and the genotyped single nucleotide polymorphisms in relation to the gene. Full boxes depict exons and empty boxes represent untranslated regulatory regions, according to public databases.
Figure 2
Figure 2
Plot of odds ratios of association analysis of LTA4H and ALOX5AP single-nucleotide polymorphisms (SNPs) and LTA4H-ALOX5AP gene-gene interaction with asthma in Mexicans, Puerto Ricans, and combined Mexicans and Puerto Ricans. Error bars indicate 95% confidence intervals.
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