Int J Immunogenet. 2018;1–7. wileyonlinelibrary.com/journal/iji | 1 © 2018 John Wiley & Sons Ltd Received: 4 May 2017 | Revised: 22 January 2018 | Accepted: 22 March 2018 DOI: 10.1111/iji.12365 ORIGINAL ARTICLE Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis L. E. Fodor 1 | A. Gézsi 1 | Z. Gál 1 | A. Nagy 2 | A. Kiss 2 | A. Bikov 3 | C. Szalai 1,2 1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary 2 Heim Pal Children Hospital, Budapest, Hungary 3 Department of Pulmonology, Semmelweis University, Budapest, Hungary Correspondence Csaba Szalai, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. Email: szalaics@gmail.com Funding information Nemzeti Kutatási és Technológiai Hivatal, Grant/Award Number: TECH_08-A1/2-2008-0120; Országos Tudományos Kutatási Alapprogramok, Grant/Award Number: K112872 and K81941 Summary The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an impor- tant role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The objective of the present study was to investigate whether varia- tions in the TEK gene influenced the susceptibility to pediatric asthma and/or associ- ated phenotypes like GINA status, viral- or exercise-induced asthma, allergic asthma, indoor, outdoor, inhalative allergies, IgE and eosonophil levels, allergic rhinitis and allergic conjunctivitis. Three single nucleotide polymorphisms (SNPs, rs3780315, rs581724 and rs7876024) in the TEK gene were genotyped in 1189 unrelated indi- viduals, out of which 435 were asthmatic children and 754 healthy controls. Different types of asthma, allergies and co-morbidities were defined in 320 patients. Among the fully phenotyped 320 asthmatic patients 178 (55.6%) also had allergic rhinitis and 100 (31.3%) had conjunctivitis. Among the rhinitis patients 98 (55.1%) also had con- junctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly asso- ciated with allergic conjunctivitis in a recessive way (p=0.007; OR=2.3 (1.3-4.4)) within the asthmatic population. The risk remained significant when the whole popu- lation (asthmatics and healthy controls) was included in the calculation (p = 0.003; OR = 2.1 (1.3-3.6)). The minor allele of the rs581724 SNP which is associated with the increased risk to conjunctivitis is also associated with reduced Tie2 expression. There was a significant association between SNP rs581724 and the occurrence of allergic conjunctivitis in asthmatic children. If additional studies can confirm the role of the Tie2 pathway in allergic conjunctivitis, it can be a potential novel therapeutic target in the disease. KEYWORDS allergic conjunctivitis, allergy, angiogenesis, asthma, genetics, Tie2 1 | INTRODUCTION Asthma is a chronic respiratory disease influenced by a wide range of environmental and genetic factors. It is characterized by coughing, wheezing, bronchoconstriction, airway hyperresponsiveness or air- way remodelling. Processes such as cytokine production, inflamma- tory cell infiltration to the lungs and injury to epithelial cells play a role in the development and severity of asthma. Structural changes