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


CONCLUSIONS
Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.
Via
M
M
Lung Biology Center, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. marc.viagarcia@ucsf.edu <marc.viagarcia@ucsf.edu>
De Giacomo
A
A
Corvol
H
H
Eng
C
C
Seibold
M A
MA
Gillett
C
C
Galanter
J
J
Sen
S
S
Tcheurekdjian
H
H
Chapela
R
R
Rodríguez-Santana
J R
JR
Rodríguez-Cintrón
W
W
Thyne
S
S
Avila
P C
PC
Choudhry
S
S
González Burchard
E
E
D058927:5-Lipoxygenase-Activating Proteins; D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D017058:Mexican Americans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase