Background: The
cysteinyl
leukotrienes (cys-LTs)
are proinfl ammatory
mediators
synthesized through
the 5-lipoxygenase
pathway of
arachidonic acid
metabolism. Cys-LTs
exert their
biological action by
binding two types of
G-protein-coupled
seven transmembrane
receptors, CYSLTR1
and CYSLTR2. The
contribution of the
cys-LT receptors to
bronchial asthma has
been established by
the therapeutic effi
cacy of biosynthetic
inhibitors and
selective CYSLTR1
blockers.
Objective:
The present study
was designed to
analyse two
different
polymorphisms 927T>C
CYSLTR1 and -444A>C
LTC4S, and to
determine whether
there is an
association between
these polymorphisms
and the asthma
phenotype in a
Spanish population.
Methods: Both
single nucleotide
polymorphisms (SNPs)
were analysed in 208
individuals (130
asthmatic subjects
and 78 controls). A
standardized history,
physical examination,
skin prick tests and
lung function
measurement were
taken from all
patients. Genotypes
were determined by
direct sequencing
after polymerase
chain reaction (PCR)
amplification.
Results: In
the group of male
patients, the C
allele of 927T > C
CYSLTR1 was more
common among
patients with asthma
than controls. No
association was
detected between the
- 444A> C LTC4S
polymorphism and the
asthma phenotype.
The combination of
927T CYSLTR1 and -
444A LTC4S was less
common in male
patients with asthma
than in controls
(Fisher´s P-value =
. 039; Monte Carlo
P-value (after 104
simulations) = .045
and the combination
of 927C CYSLTR1 and
- 444A LTC4S was
slightly more
frequent in patients
with asthma. No
differences were
observed in the
female group.
Conclusions:
The results suggest
a certain trend of
associations that
could help to
explain some
controversial
results in
association studies
of these genes from
the leukotriene
pathway, when
considered
individually.
Further studies are
needed to confi rm
such an association.
Key words:
Asthma. Gene. CYSLT.
LTC4. Leukotrienes.
Polymorphism. |