Dataset Information

Investigation of the Possible Role of Tie2 Pathway and TEK Gene in Asthma and Allergic Conjunctivitis.

ABSTRACT: Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. The discovery, stage I cohort involved 306 patients with moderate and severe allergic rhinitis, the stage II study consisted of four cohorts, namely, adult and pediatric asthmatics and corresponding controls. Altogether, there were 1,258 unrelated individuals in these cohorts, out of which 63.9% were children and 36.1% were adults. In stage I, 112 SNPs were screened in the TEK gene of the patients in order to search for associations with asthma and allergic conjunctivitis. The top associated SNPs were selected for association studies on the replication cohorts. The rs3824410 SNP was nominally associated with a reduced risk of asthma in the stage I cohort and with severe asthma within the asthmatic population (p=0.009; OR=0.48) in the replication cohort. In the stage I study, 5 SNPs were selected in conjunctivitis. Due to the low number of adult patients with conjunctivitis, only children were involved in stage II. Within the asthmatic children, the rs622232 SNP was associated with conjunctivitis in boys in the dominant model (p=0.004; OR=4.76), while the rs7034505 showed association to conjunctivitis in girls (p=0.012; OR=2.42). In the lung of a mouse model of asthma, expression changes of 10 Tie2 pathway-related genes were evaluated at three points in time. Eighty percent of the selected genes showed significant changes in their expressions at least at one time point during the process, leading from sensitization to allergic airway inflammation. The expressions of both the Tek gene and its ligands showed a reduced level at all time points. In conclusion, our results provide additional proof that the Tie2 pathway, the TEK gene and its variations might have a role in asthma and allergic conjunctivitis. The gene and its associated pathways can be potential therapeutic targets in both diseases.

SUBMITTER: Gal Z

PROVIDER: S-EPMC7057532 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Investigation of the Possible Role of Tie2 Pathway and TEK Gene in Asthma and Allergic Conjunctivitis.

Gál Zsófia Z Gézsi András A Molnár Viktor V Nagy Adrienne A Kiss András A Sultész Monika M Csoma Zsuzsanna Z Tamási Lilla L Gálffy Gabriella G Bálint Bálint L BL Póliska Szilárd S Szalai Csaba C

Frontiers in genetics 20200227

Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. The discovery, stage I cohort involved 306 patients with moderate and severe allergic rhin ...[more]

PMID: 32180797

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Project description:BackgroundSingle nucleotide polymorphisms (SNPs) in the interleukin 13 (IL13) gene are associated with vulnerability to allergic diseases, such as asthma and allergic conjunctivitis (AC). Periostin, as an IL13-induced protein, has emerged as a novel biomarker in several allergic diseases. Data among Egyptian patients are still scarce.AimTo find out the association of IL13 rs20541 gene polymorphism and serum levels of periostin with asthma and AC among Egyptian patients.Patients and methodsEighty-one Egyptian allergic patients with asthma, AC, and both asthma and AC (27 each), were enrolled in this case-control study. Twenty-seven age and gender-matched healthy volunteers served as controls. All participants were tested for IL13 rs20541 SNP by real-time polymerase chain reaction, TaqMan method. Serum levels of periostin and IL13 were assessed by ELISA.ResultsCompared to healthy subjects, asthmatic patients had a higher frequency of the homozygous adenine/adenine (AA) genotype at IL13 rs20541 SNP (14.8% vs 3.7%) and a lower frequency of the guanosine/guanosine (GG) genotype (51.9% vs 55.6%), while AC patients had higher GG genotype (70.4% vs 55.6%) with no AA genotype detected, yet no significant difference was noticed (p = 7.053). A significantly higher serum periostin in asthmatic patients compared to controls was found (p = 0.005). Higher levels of serum periostin, although nonsignificant, were recorded in AC patients compared to controls (22.88 ± 10.01ng/mL and 17.51 ± 3.17ng/mL, respectively). Periostin was significantly higher in patients with IL13 AA and GA genotypes compared to those with GG genotype (p = 0.016). A significant positive correlation between serum periostin and serum IL13 among allergic patients was recorded (r = 0.352, p < 0.001).ConclusionAmong Egyptian patients, serum level of periostin is significantly associated with asthma and positively correlates with IL13 level supporting its utility as a diagnostic biomarker. IL13 rs20541 gene polymorphism does not seem to play an obvious role in asthma and AC, which requires further evaluation.

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Dataset Information

Investigation of the Possible Role of Tie2 Pathway and TEK Gene in Asthma and Allergic Conjunctivitis.

Publications

Investigation of the Possible Role of Tie2 Pathway and <i>TEK</i> Gene in Asthma and Allergic Conjunctivitis.

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