INTRODUCTION
Preschool wheeze (PSW) is a highly prevalent clinical
problem1 that presents within a wide spectrum of
severity and is associated with considerable healthcare
costs2. Asthma has its origins in early childhood;
however, different patterns of childhood wheezing vary in their
association with subsequent asthma, atopy, and bronchial
hyper-responsiveness. Wheezing phenotypes used in epidemiological
studies are frequently defined retrospectively and are therefore not
usable in clinical practice3. In 2008, the European
Respiratory Society’s preschool study group divided wheezing phenotypes
into episodic (viral) wheeze (EW) and multiple-trigger wheeze
(MW)4. According to this classification, wheezing
attacks triggered only by viral respiratory tract infections with no
complaints between attacks are classified as EW. Wheezing attacks
triggered by allergens, exercise, cold weather conditions, or smoke, in
addition to viral respiratory tract infections, with complaints between
attacks are classified as MW4. However, wheeze
patterns in young children vary over time and with treatment, rendering
the distinction between EW and MW unclear in many
patients5. Therefore, we need predictive markers that
are useful for differentiating between wheezing phenotypes and
predicting asthma development in children with PSW as a guide for
clinicians in early treatment decision-making.
There has been increasing interest among researchers to find a
relationship between different genes and wheezing phenotypes and
persistence and the development of childhood
asthma6,7. Arginase (ARG ) genes have been
investigated in this context. Arginase, an essential enzyme in the
hepatic urea cycle, is involved in L-arginine homeostasis by catalyzing
the reaction in which L-arginine is converted to L-ornithine and urea.
Arginase is also expressed in nonhepatic tissues, including in the
airways. In humans, two arginase isoenzymes have been identified,
arginase 1 and arginase 2, and both are constitutively expressed in the
airways. Arginase and nitric oxide synthases (NOS) compete for their
common substrate, L-arginine. Increased arginase expression and low
L-arginine levels have been found to be associated with asthma and
airway remodeling8-12. After defining the important
contributions of arginase in asthma, genetic studies have attempted to
identify an association between genetic variation in ARG genes
and susceptibility for asthma, atopic sensitization, and bronchodilator
response (BDR) in different populations13-21. These
studies have reported many associations between different single
nucleotide polymorphisms (SNPs) in ARG1 or ARG2 genes and
atopic sensitization13, 15, risk of
asthma13, 16,21, asthma severity16,
bronchodilator/steroid response in asthma14, 16,
19,20, and the arginase-NOS pathway 17,18, although
some of these results have not been replicated.
To date, associations between polymorphisms in ARG genes and PSW
phenotypes are unknown. Therefore, this study aimed to investigate
whether there is any relationship between polymorphisms in ARGgenes and PSW phenotypes among Turkish children and compare these
results with those of asthmatic children over five years old.