IL13, IL17A and GSTP1 polymorphisms" name="citation_title" /> Asthma and rhinitis have different genetic profiles for <span class="elsevierStyleItalic">IL13</span>, <span class="elsevierStyleItalic">IL17A</span> and <span class="elsevierStyleItalic">GSTP1</span> polymorphisms
Original article
Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms
E.P. Resendea,, , A. Todo-Bomb,d, C. Loureirob, A. Mota Pintoc,d, B. Oliveirose, L. Mesquitaa, H.C. Silvaa,d
a Genetics Institute, Faculty of Medicine, University of Coimbra, Portugal
b Immunoallergology Department, Coimbra University Hospital, Portugal
c Laboratory of General Pathology, Faculty of Medicine, University of Coimbra, Portugal
d CIMAGO – Centre of Investigation of Environment, Genetics and Oncobiology, Coimbra, Portugal
e Laboratory for Biostatistics and Medical Informatics, Faculty of Medicine, University of Coimbra, Portugal
Received 29 March 2016, Accepted 27 June 2016

Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds.


To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry.


192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays.


Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) – 1.96; 95% CI – 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR – 2.17; 95% CI – 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR – 0.55, 95% CI – 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR – 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR – 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism’ analyzed.


These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.

Asthma, Rhinitis, Allergy, IL4R, IL13, IL17A, GSTP1, Genetic polymorphism, Genetic profile

Asthma and asthma-related disorders, such as sinusitis and rhinitis, are complex diseases with strong genetic and environmental components.1 Over the last decades their prevalence has been increasing worldwide, with a significant economic impact on health services.

Asthma is a common chronic inflammatory disease of the lower airways, characterized by reversible airflow obstruction, inflammation, persistent hyper-reactivity and airway remodeling.2 Rhinitis is an upper airways inflammatory disease, often associated with asthma3 and have been recognized as a risk factor for its development and severity.4

Genetic contribution to these phenotypes may account for 50–60%,5,6 so dissecting genetic susceptible profiles may provide insight into the pathogenesis, allowing us to identify different sub-phenotypes and also contribute to finding new targeted therapies.

An increasing number of asthma susceptibility loci are continuously being identified, either by candidate gene studies or, more recently, by microarray-based whole genome approach, the genome-wide association (GWA) studies. Results are hampered by difficulties common to other complex diseases: inconsistent replication of results, functional association between identified loci and phenotype is not obvious, and most of all, allele penetrance is low and phenotype variance largely remains to be explained.7–10 Most marker SNPs (single nucleotide polymorphisms) are localized in or near-by genes encoding proteins directly or indirectly involved in immunologic response. Recently, GWAs have revealed that different allergic diseases with common immunological physiopathology, also share susceptibility loci.10

Interleukin-4 (IL4) mediates important pro-inflammatory functions in allergic phenotypes and has principle responsibility for the IgE isotype switch by B lymphocytes.11 IL4 is also involved in T helper type 2 (TH2) lymphocytes activation, induction of endothelium modifications, hypersecretion of mucus and with lung remodeling in chronic asthma.11 IL4 action is mediated through activation of its receptor IL4R, a cell-surface heterodimeric complex.

Interleukin-13 (IL13) is one of the cytokines released by IL4 mediated Th2 induced cells and shares most of IL4 functions. IL13 production in the airway promotes the survival and migration of eosinophils, activation of macrophages, increased permeability and mucus production by airway epithelial cells and stimulates airways hyperresponsiveness.12 Huang et al.13 found that asthmatic and rhinitis patients submitted to allergen-challenge had a significant enhancement of IL13 gene expression at mRNA and protein levels in bronchoalveolar lavage samples compared with the saline-challenged control sites.

Interleukin-17A (IL17A) is the best studied member of IL17 family of cytokines. It is mainly produced by activated T cells. Signaling through activation NF-kappaB and mitogen-activated protein kinases, IL17A regulates local tissue inflammation inducing the expression of pro-inflammatory cytokines, neutrophil-recruiting chemokines, cyclooxygenase-2 (COX2) and nitric oxide (NO). IL17A may also modulate the activation and proliferation of B cells, thus enhancing IgE production and has been associated with airway hyperresponsiveness and remodeling.14,15

SNPs from IL4, IL4R and IL13 genes are among the polymorphisms most frequently implicated in susceptibility to asthma, rhinitis and allergic phenotypes in general,16 with some of these SNPs being associated with increased serum IgE levels.17,18 Up to now few studies are available on the association with genetic polymorphisms of IL17A family members.19–21

Reactive oxygen and nitrogen species, originated from air pollutants or released by inflammatory cells and stressed bronchial epithelia, are major contributors to asthma and asthma related phenotypes.22 Glutathione-S-transferases (GSTs) are enzymes involved in the cellular detoxification of free radicals. A missense SNP in Glutathione S-transferase P1 (GSTP1), rs1695 (p.Ile105Val), has been associated with differences in enzyme activity and susceptibility to environmental-induced diseases, including asthma, but results remain controversial.23,24

Frequencies of DNA polymorphisms vary between populations of diverse ethnical origins, as their contributions to complex diseases, therefore, it is important to study different populations. In this study we evaluate the role of IL4R rs1805015, IL13 rs20541, IL17A rs2275913 and GSTP1 rs1695 in the susceptibility to asthma and rhinitis in an adult population of Portuguese ancestry.

Materials and methodsClinical samples

This case–control study comprises 424 non related Caucasian Portuguese individuals, including 232 patients and 192 controls, randomly selected from a larger sample that answered a home inquiry about symptoms of asthma, rhinitis and sinusitis. Individuals willing to participate were than observed at the Immunoallergology Department of Coimbra University Hospitals.

The patient population was subdivided into two groups, according to the clinical diagnosis, using ARIA (Allergic Rhinitis and Its Impact On Asthma),4 GINA (Global Initiative for Asthma)2 and EP3OS (European Position Paper on Rhinosinusitis and Nasal Polyps 2007)25 criteria: one group including patients with rhinitis but no asthma and another group including patients with persistent asthma, which could also have rhinitis. As explained in “Results” section, patients with both rhinitis and asthma were grouped with those who only had asthma. Controls had no symptoms related to respiratory system and no history of any allergic disease. Other known inflammatory or chronic conditions, including cancer, were exclusion criteria for both patients and controls. A skin prick test for 17 different inhalant allergens, selected according to the recommendations of the GA2LEN (Global Asthma and Allergy European Network),26 was performed on all patients and those who had at least one positive result were considered allergic. The test was considered positive when wheal diameter was ≥3mm and controls showed sufficient reaction.26 Participants were considered allergic only in the presence of both symptoms and a positive skin prick test. The local ethics committee approved the study and patients provided informed consent.


DNA was extracted from 5ml of frozen peripheral blood by standard methods. Characterization of the four SNPs was achieved by real time polymerase chain reaction (PCR) using the TaqMan assays (Applied Biosystems), iQTM Supermix (Bio-Rad Laboratories) and 10–30ng of DNA, in a 7500 Fast Real-Time PCR System (Applied Biosystems). As positive controls, we used samples previously genotyped by automatic sequencing in an AbiPrism 3130 Genetic Analyser using BD v1.1 (Applied Biosystems) and Sequencing Analysis Software v5.2. The description of the four SNPs, the primers used in sequencing and TaqMan assay references are depicted in Table 1.

Table 1.

SNPs evaluated.

Gene  SNP  Primer sequencea  TaqMan assay ID 
IL4R  rs1805015; TCC>CCC
missense (p.Ser503Pro) 
IL13  rs20541; CAG>CGG
missense (p.Gln144Arg) 
IL17A  rs2275913; −197G>Ab
(regulatory region) 
GSTP1  rs1695;
missense (p.Ile105Val) 

Primers used in genotyping by sequencing.



Statistical analysis

Statistical analysis was developed using the IBM® program SPSS® (Statistical Package for Social Sciences) version 20. Fisher exact-test, χ2 was applied to analyze the difference between the three groups. Logistic regression models were used to control for potential confounders and to evaluate the associations between the risk of disease and genetic polymorphisms. All odds ratios (ORs) with 95% confidence intervals (CI) were adjusted for age, sex and smoking habits and p<0.05 was considered statistically significant. When comparing rhinitis and asthma patients, ORs were also adjusted for atopy.


A preliminary analysis revealed that for distribution of SNP variants, smoking habits and atopy (positive skin prick test results), there were no statistically significant differences between patients associating asthma and rhinitis and patients only with asthma (Supplementary Table 1). For this reason, and because asthma is considered a more aggressive phenotype, the two groups were joined together, so patients were further on classified as having rhinitis or asthma, as described in Table 2. The cohort of 83 patients with rhinitis had a mean age of 48.50 years (SD=15.17) and 63.9% females. The group of 149 asthmatic patients was younger, with a mean age of 39.32 years (SD=14.04) and 66.4% were females. The control group had a mean age of 56.06 years (SD=19.48) and 52.1% females. According to results of skin prick test, allergy was more frequent among asthmatic patients (78.5%; Table 2).

Table 2.

Characteristics of patients and controls.

n=83 (%) 
n=149 (%) 
n=192 (%) 
Male  30 (36.1)  50 (33.6)  92 (47.9)  0.005
Female  53 (63.9)  99 (66.4)  100 (52.1) 
Age (years)
Mean (SD)  48.50 (15.17)  39.32 (14.04)  56.06 (19.48)  <0.001 
Smoking habits
No smoking  54 (65.9)  104 (71.2)  121 (64.4)  NS
Smoking  28 (34.1)  42 (28.8)  67 (35.6) 
Skin test positivea  40 (48.2)  117 (78.5)  NA  <0.001 

Test with at least one positive result.

NA – not available.

SD – standard deviation.

NS – without statistical significance.

The Hardy–Weinberg equilibrium was verified for the four polymorphisms (p>0.05). The frequency of GSTP1 rs1695 AA genotype was significantly higher in patients with asthma than in controls (49.0% vs. 33.9%; OR – 1.96, 95% CI – 1.18 to 3.25; p=0.010) (Table 3). When only considering patients with allergic asthma (data not shown) results were similar (OR – 2.17, 95% CI – 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was significantly less prevalent in asthma cases (62.6%) than in controls (70.8%) (OR – 0.55, 95% CI – 0.33 to 0.94; p=0.028) (Table 3).

Table 3.

Comparative study of genotypic frequencies in controls and patients.

n (%) 
n (%) 
p-Valuea  Asthma
n (%) 
p-Valueb  AdjORc,b
(95% CI) 
GSTP1 rs1695
Ile/Ile (AA)  65 (33.9)  35 (42.2)  0.260  73 (49.0)  0.010  1.96 (1.18–3.25) 
Ile/Val (AG)  97 (50.5)  40 (48.2)  0.849  61 (40.9)  0.418   
Val/Val (GG)  30 (15.6)  8 (9.6)  0.202  15 (10.1)  0.418   
IL13 rs20541
Arg/Arg (GG)  136 (70.8)  60 (73.2)  0.686  92 (62.6)  0.028  0.55 (0.33–0.94) 
Gln/Arg (AG)  52 (27.1)  20 (24.4)  0.694  50 (34.0)  0.908   
Gln/Gln (AA)  4 (2.1)  2 (2.4)  0.948  5 (3.4)  0.908   
IL17 rs2275913
GG  94 (49.0)  28 (33.7)  0.068  69 (46.6)  0.552   
AG  81 (42.2)  41 (49.4)  0.532  71 (48.0)  0.978   
AA  17 (8.9)  14 (16.9)  0.072  8 (5.4)  0.230   
IL4R rs1805015
Ser/Ser (TT)  140 (73.3)  65 (78.3)  0.374  115 (77.2)  0.939   
Ser/Pro (TC)  43 (22.5)  15 (18.1)  0.447  30 (20.1)  0.614   
Pro/Pro (CC)  8 (4.2)  3 (3.6)  0.707  4 (2.7)  0.199   

Controls vs rhinitis


Controls vs asthma


AdjOR – Adjusted Odds Ratio for age, gender and smoking habits.

Among patients, IL13 rs20541 GG genotype was less frequently associated with asthma than with rhinitis (OR – 0.48, 95% CI – 0.25 to 0.93; p=0.031)(Table 4). The IL17A rs2275913 AA genotype was also significantly less frequent in asthmatic patients (5.4%) than in rhinitis patients (16.9%)(OR – 0.20, 95% CI – 0.07 to 0.56; p=0.002) (Table 4).

Table 4.

Comparative study of IL17A and IL13 polymorphisms genotypic frequencies between the two patient groups.

n (%) 
n (%) 
p-Value  AdjOR (95% CI)a 
IL13 rs20541
Arg/Arg (GG)  60 (73.2)  92 (62.6)  0.031  0.48 (0.25–0.93) 
Gln/Arg (AG)  20 (24.4)  50 (34.0)  0.797   
Gln/Gln (AA)  2 (2.4)  5 (3.4)  0.797   
IL17 rs2275913
GG  28 (33.7)  69 (46.6)  0.97   
AG  41 (49.4)  71 (48.0)  0.97   
AA  14 (16.9)  8 (5.4)  0.002  0.20 (0.07–0.56) 

AdjOR – Adjusted Odds Ratio for age, gender, atopy and smoking habits.

For the IL4R and GSTP1 polymorphism’ analyzed, there were no significant differences in the distribution of genotypic frequencies between patients.

For IL4R rs1805015, there were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls (Table 3) or between the two disease phenotypes (data not shown).


In this work we evaluate the role of polymorphisms of four genes, IL4R, IL13, IL17A, and GSTP1 in the susceptibility to two related phenotypes, asthma and rhinitis.

As expected,27 patients were mostly of female gender. In agreement with previous studies,28 our results suggest that most patients with asthma have allergen sensitization.

Comparing patients and controls, GSTP1 rs1695 AA genotype conferred about twofold risk for developing asthma and allergic asthma. These results of a Portuguese population are in accordance with previous studies that have associated the A variant with a higher risk,29 or the G (Val) variant with a lower risk30,31 to develop asthma and allergic phenotypes. Yet a meta-analysis23 only suggested a possible, weak protective effect of the G (Val) allele. Like other authors, we found no evidence of a correlation between GSTP1 SNP and rhinitis.32

GSTs play important roles in airway antioxidant defenses33 and GSTP1 enzyme contributes to more than 90% of GST-derived enzyme activity in human lung epithelium.34 The rs1695 SNP has been associated with differences in GSTP1 substrate affinities.35 A recent study36 showed that asthma patients who have homozygosity for A (Ile) allele are more likely to be affected by air pollutants. These findings substantiate the functional relevance of the SNP,37 and support our results. Yet, we are aware that this genetic effect can be affected by environment-induced epigenetic modifications that influence gene expression and ultimately, the level of enzymatic activity.38,39 Epigenetic regulation is tissue-specific and may account for some of the differences in GSTP1 role between upper and lower airways.

For IL13 SNP, our results suggest that homozygosity for G allele, corresponding to arginine (Arg) variant, may decrease susceptibility to asthma. IL13 polymorphisms have repeatedly being associated with increased IgE serum levels, allergy and asthma.16,40 The association of rs20541 with allergic rhinitis was reported in a recent meta-analysis of an Asian population.41

IL13 rs20541 (CAG>CGG) results in the non-conservative replacement of a neutral glutamine (Gln) for a positively charged arginine (Arg) in the IL13 α helix of D domain, the region that is thought to interact with IL4Rα/IL13Rα1 heterodimers.42 The A allele has been associated with increased IL13 expression43 and a lower affinity for the IL13 receptor α2 chain (IL13Rα2), which is a decoy receptor that antagonizes inflammation and tissue remodeling.44 These observations point to a lower inflammatory activity of arginine variant (G allele) comparing with glutamine (A allele), supporting the association with a decreased susceptibility to asthma.

In contrast to other studiess,17,41 we could not confirm the same correlations for rhinitis. The difference in results may be explained by the fact that upper airways patency is largely influenced by vascular tone, whereas in the lower airways, smooth muscle function is determinant.45 IL13 was shown to directly interfere with airway smooth muscle cell responsiveness by enhancing agonist-induced contractility and calcium signals, a mechanism that may be mediated by stromal interaction molecule-1 (STIM1), a sarcoplasmic reticulum protein involved in the regulation of intracellular Ca2+ concentrations.46

Comparing both groups of patients, IL17A rs2275913 AA genotype was less frequently associated with asthma than with rhinitis, reinforcing the difference between the genetic profiles of these phenotypes. This SNP is located in 5′ regulatory region, within a binding motif for the nuclear factor of activated T cells (NFAT), which is a critical regulator of the IL17A promoter. Peripheral blood level determination and gene reporter assays showed that the A variant was associated with increased levels of IL17A expression and displayed a higher affinity for NFAT.47

For rhinitis, our data concur with the functional relevance of A variant. IL17A is known to be a proinflammatory, leukocyte-derived cytokine that targets epithelial cells48 and that seems to play a central role in rhinitis.14 IL17A expression in the nasal mucosa was associated with the pathophysiology of allergic rhinitis, including disease severity and local eosinophilia.49

In asthma, increased expression of IL17A has been described mainly in severe and non-allergic forms.50,51 The majority of patients included in our study had moderate asthma, which may account for the negative association observed with the higher inflammatory activity A allele. Reinforcing our results, Lei et al.52 describe similar serum levels of IL-17A between asthmatic and normal controls. Globally, controversial results have been published, with studies suggesting that different polymorphisms of IL17A and IL17F may contribute both to susceptibility or resistance to asthma or allergic rhinitis.19–21

No significant association was observed between IL4R rs1805015 polymorphism with rhinitis or asthma. Although this association was confirmed in recent GWA studies,9 contradictory reports exist and results frequently differ between populations.16,18

The difference in results between our data and some previous reports is a common issue in complex disease research. Differences in population genetic backgrounds, in sample size and selection, phenotype classification, in environmental exposure and epigenetic mechanisms, contribute to the results divergence.

To overcome limitations of this study, in future work it will be important to enlarge the population samples to be analyzed and to define more specific and homogeneous phenotypes.


We describe the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 polymorphisms, respectively with higher and reduced susceptibility to asthma. For patients that develop reactive inflammatory respiratory diseases, IL17A rs2275913 and IL13 rs20541 polymorphisms influence the predominant upper airways (rhinitis) or lower airways (asthma) clinical pattern. These results also support the hypothesis that the genetic susceptibility profiles of asthma and isolate chronic rhinitis are not equivalent.

Ethical disclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data

The authors declare that they have followed the protocols of their work center on the publication of patient data.

Right to privacy and informed consent

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.

Conflicts of interest

None of the authors have any conflicts of interest to declare.


The authors are grateful to Centre of Pneumology for funding this work.

D. Vercelli
Discovering susceptibility genes for asthma and allergy
Nat Rev Immunol, 8 (2008), pp. 169-182
E.D. Bateman,S.S. Hurd,P.J. Barnes,J. Bousquet,J.M. Drazen,M. FitzGerald
Global strategy for asthma management and prevention: GINA executive summary
Eur Respir J, 31 (2008), pp. 143-178
J. Eriksson,A. Bjerg,J. Lotvall,G. Wennergren,E. Ronmark,K. Toren
Rhinitis phenotypes correlate with different symptom presentation and risk factor patterns of asthma
Respir Med, 105 (2011), pp. 1611-1621
J. Bousquet,N. Khaltaev,A.A. Cruz,J. Denburg,W.J. Fokkens,A. Togias
Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)
S.F. Thomsen,S. van der Sluis,K.O. Kyvik,A. Skytthe,V. Backer
Estimates of asthma heritability in a large twin sample
Clin Exp Allergy, 40 (2010), pp. 1054-1061
S.E. Wenzel
Asthma phenotypes: the evolution from clinical to molecular approaches
Nat Med, 18 (2012), pp. 716-725
S. Undarmaa,Y. Mashimo,S. Hattori,N. Shimojo,K. Fujita,A. Miyatake
Replication of genetic association studies in asthma and related phenotypes
J Hum Genet, 55 (2010), pp. 342-349
E. Bouzigon,P. Forabosco,G.H. Koppelman,W.O. Cookson,M.H. Dizier,D.L. Duffy
Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy
Eur J Hum Genet, 18 (2010), pp. 700-706
M.F. Moffatt,I.G. Gut,F. Demenais,D.P. Strachan,E. Bouzigon,S. Heath
A large-scale, consortium-based genomewide association study of asthma
N Engl J Med, 363 (2010), pp. 1211-1221
M. Tamari,S. Tanaka,T. Hirota
Genome-wide association studies of allergic diseases
J.W. Steinke,L. Borish
Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists
Respir Res, 2 (2001), pp. 66-70
J.L. Ingram,M. Kraft
IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies
J Allergy Clin Immunol, 130 (2012), pp. 829-842
[quiz 843-824]
S.K. Huang,H.Q. Xiao,J. Kleine-Tebbe,G. Paciotti,D.G. Marsh,L.M. Lichtenstein
IL-13 expression at the sites of allergen challenge in patients with asthma
J Immunol, 155 (1995), pp. 2688-2694
Y. Liu,M. Zeng,Z. Liu
Th17 response and its regulation in inflammatory upper airway diseases
Clin Exp Allergy, 45 (2015), pp. 602-612
D.C. Newcomb,R.S. Peebles Jr.
Th17-mediated inflammation in asthma
Curr Opin Immunol, 25 (2013), pp. 755-760
Z.D. Wang,D. Lian,J.L. Shen,R. Sun,W. Xu,Z. Xin
Association between the interleukin-4, interleukin-13 polymorphisms and asthma: a meta-analysis
Mol Biol Rep, 40 (2013), pp. 1365-1376
R.W. Bottema,I.M. Nolte,T.D. Howard,G.H. Koppelman,A.E. Dubois,G. de Meer
Interleukin 13 and interleukin 4 receptor-alpha polymorphisms in rhinitis and asthma
Int Arch Allergy Immunol, 153 (2010), pp. 259-267
W. Nie,Y. Liu,J. Bian,B. Li,Q. Xiu
Effects of polymorphisms −1112C/T and +2044A/G in interleukin-13 gene on asthma risk: a meta-analysis
M.D. Bazzi,M.A. Sultan,N. Al Tassan,M. Alanazi,A. Al-Amri,M.S. Al-Hajjaj
Interleukin 17A and F and asthma in Saudi Arabia: gene polymorphisms and protein levels
J Investig Allergol Clin Immunol, 21 (2011), pp. 551-555
M. Wang,Y. Zhang,D. Han,L. Zhang
Association between polymorphisms in cytokine genes IL-17A and IL-17F and development of allergic rhinitis and comorbid asthma in Chinese subjects
Hum Immunol, 73 (2012), pp. 647-653
Y. Jin,Z. Deng,C. Cao,L. Li
IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms
I. Rahman,S.K. Biswas,A. Kode
Oxidant and antioxidant balance in the airways and airway diseases
Eur J Pharmacol, 533 (2006), pp. 222-239
C. Minelli,R. Granell,R. Newson,M.J. Rose-Zerilli,M. Torrent,S.M. Ring
Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data
Int J Epidemiol, 39 (2010), pp. 539-562
S. Piacentini,R. Polimanti,I. Simonelli,S. Donno,P. Pasqualetti,D. Manfellotto
Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis
Mol Biol Rep, 40 (2013), pp. 3299-3313
W. Fokkens,V. Lund,J. Mullol,European Position Paper on Rhinosinusitis and Nasal Polyps Group
European position paper on rhinosinusitis and nasal polyps 2007
Rhinol Suppl, (2007), pp. 1-136
L.M. Heinzerling,G.J. Burbach,G. Edenharter,C. Bachert,C. Bindslev-Jensen,S. Bonini
GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe
M. Schatz,C.A. Camargo Jr.
The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organization
Ann Allergy Asthma Immunol, 91 (2003), pp. 553-558
T.J. Craig
Aeroallergen sensitization in asthma: prevalence and correlation with severity
Allergy Asthma Proc, 31 (2010), pp. 96-102
M. Imboden,T. Rochat,M. Brutsche,C. Schindler,S.H. Downs,M.W. Gerbase
Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults
A.S. Aynacioglu,M. Nacak,A. Filiz,E. Ekinci,I. Roots
Protective role of glutathione S-transferase P1 (GSTP1) Val105Val genotype in patients with bronchial asthma
Br J Clin Pharmacol, 57 (2004), pp. 213-217
C. Hanene,L. Jihene,A. Jamel,H. Kamel,H. Agnes
Association of GST genes polymorphisms with asthma in Tunisian children
Mediat Inflamm, 2007 (2007), pp. 19564
A. Iorio,R. Polimanti,S. Piacentini,G.M. Liumbruno,D. Manfellotto,M. Fuciarelli
Deletion polymorphism of GSTT1 gene as protective marker for allergic rhinitis
I. Rahman,W. MacNee
Oxidative stress and regulation of glutathione in lung inflammation
Eur Respir J, 16 (2000), pp. 534-554
A.A. Fryer,R. Hume,R.C. Strange
The development of glutathione S-transferase and glutathione peroxidase activities in human lung
Biochim Biophys Acta, 883 (1986), pp. 448-453
M.A. Watson,R.K. Stewart,G.B. Smith,T.E. Massey,D.A. Bell
Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution
Carcinogenesis, 19 (1998), pp. 275-280
M.W.H. Sada,T. Inui,K. Nakamoto,K. Honda,M. Nakamura,M. Horie,Y. Mikami,S. Noguchi,H. Takizawa
Influence of air pollutants and glutathione S-transferase P1 gene polymorphism in patients with bronchial asthma
J.D. Hayes,R.C. Strange
Glutathione S-transferase polymorphisms and their biological consequences
Pharmacology, 61 (2000), pp. 154-166
R.L. Miller,S.M. Ho
Environmental epigenetics and asthma: current concepts and call for studies
Am J Respir Crit Care Med, 177 (2008), pp. 567-573
F. Child,W. Lenney,S. Clayton,S. Davies,P.W. Jones,J.E. Alldersea
The association of maternal but not paternal genetic variation in GSTP1 with asthma phenotypes in children
Respir Med, 97 (2003), pp. 1247-1256
A. Heinzmann,X.Q. Mao,M. Akaiwa,R.T. Kreomer,P.S. Gao,K. Ohshima
Genetic variants of IL-13 signalling and human asthma and atopy
Hum Mol Genet, 9 (2000), pp. 549-559
X.J. Ying,S.W. Zhao,G.L. Wang,J. Xie,H.M. Xu,P. Dong
Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: a meta-analysis
A.B. Madhankumar,A. Mintz,W. Debinski
Alanine-scanning mutagenesis of alpha-helix D segment of interleukin-13 reveals new functionally important residues of the cytokine
J Biol Chem, 277 (2002), pp. 43194-43205
K. Arima,R. Umeshita-Suyama,Y. Sakata,M. Akaiwa,X.Q. Mao,T. Enomoto
Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma
J Allergy Clin Immunol, 109 (2002), pp. 980-987
E.R. Lacy
Equilibrium and kinetic analysis of human interleukin-13 and IL-13 receptor alpha-2 complex formation
J Mol Recognit, 25 (2012), pp. 184-191
J. Rimmer,J.W. Ruhno
6: Rhinitis and asthma: united airway disease
Med J Aust, 185 (2006), pp. 565-571
L. Jia,P. Delmotte,B. Aravamudan,C.M. Pabelick,Y.S. Prakash,G.C. Sieck
Effects of the inflammatory cytokines TNF-alpha and IL-13 on stromal interaction molecule-1 aggregation in human airway smooth muscle intracellular Ca(2+) regulation
Am J Respir Cell Mol Biol, 49 (2013), pp. 601-608
J.L. Espinoza,A. Takami,K. Nakata,M. Onizuka,T. Kawase,H. Akiyama
A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation
S. Eyerich,K. Eyerich,A. Cavani,C. Schmidt-Weber
IL-17 and IL-22: siblings, not twins
Trends Immunol, 31 (2010), pp. 354-361
S. Makihara,M. Okano,T. Fujiwara,Y. Noda,T. Higaki,T. Miyateke
Local expression of interleukin-17a is correlated with nasal eosinophilia and clinical severity in allergic rhinitis
Allergy Rhinol (Providence), 5 (2014), pp. 22-27
I. Agache,C. Ciobanu,C. Agache,M. Anghel
Increased serum IL-17 is an independent risk factor for severe asthma
Respir Med, 104 (2010), pp. 1131-1137
Y.H. Wang,M. Wills-Karp
The potential role of interleukin-17 in severe asthma
Curr Allergy Asthma Rep, 11 (2011), pp. 388-394
Z. Lei,G. Liu,Q. Huang,M. Lv,R. Zu,G.M. Zhang
SCF and IL-31 rather than IL-17 and BAFF are potential indicators in patients with allergic asthma
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  • 5-years Impact Factor: 0,841
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