Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis

L.E. Fodor; A. Gézsi; Z. Gál; A. Nagy; A. Kiss; A. Bikov; C. Szalai

doi:10.1111/iji.12365

Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis

L.E. Fodor, A. Gézsi, Z. Gál, A. Nagy, A. Kiss, A. Bikov, C. Szalai

Division of Immunology, Immunity to Infection and Respiratory Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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 important 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 variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated 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 individuals, 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 conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated 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 population (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. © 2018 John Wiley & Sons Ltd

Original language	English
Pages (from-to)	102-108
Number of pages	7
Journal	International Journal of Immunogenetics
Volume	45
Issue number	3
Early online date	18 Apr 2018
DOIs	https://doi.org/10.1111/iji.12365
Publication status	Published - 2018

Keywords

allergic conjunctivitis
allergy
angiogenesis
asthma
genetics
Tie2
genomic DNA
allele
allergic asthma
Article
child
comorbidity
conjunctivitis
eosinophil count
female
gene
genetic association
genotype
human
major clinical study
male
priority journal
school child
single nucleotide polymorphism
TEK gene

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/iji.12365

Cite this

@article{f85da1cbf6014ee9af27e9cc2b0dcb53,

title = "Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis",

abstract = "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 important 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 variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated 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 individuals, 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 conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated 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 population (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. {\textcopyright} 2018 John Wiley & Sons Ltd",

keywords = "allergic conjunctivitis, allergy, angiogenesis, asthma, genetics, Tie2, genomic DNA, allele, allergic asthma, Article, child, comorbidity, conjunctivitis, eosinophil count, female, gene, genetic association, genotype, human, major clinical study, male, priority journal, school child, single nucleotide polymorphism, TEK gene",

author = "L.E. Fodor and A. G{\'e}zsi and Z. G{\'a}l and A. Nagy and A. Kiss and A. Bikov and C. Szalai",

note = "Export Date: 31 October 2018 Correspondence Address: Szalai, C.; Department of Genetics, Cell- and Immunobiology, Semmelweis UniversityHungary; email: [email protected] Funding details: NKTH, Nemzeti Kutat{\'a}si {\'e}s Technol{\'o}giai Hivatal Funding details: K81941, OTKA, Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok Funding details: K112872, OTKA, Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok Funding details: TECH_08-A1/2-2008-0120, NST, National Research Council of Science and Technology Funding details: OTKA, Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok Funding text: This study was supported by OTKA (Hungarian Scientific Research Fund): K81941, K112872 (C. Szalai); and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120: (C. Szalai). References: Almoguera, B., Vazquez, L., Mentch, F., Connolly, J., Pacheco, J.A., Sundaresan, A.S., Hakonarson, H., Identification of four novel loci in asthma in European and African American populations (2017) American Journal of Respiratory and Critical Care Medicine, 195 (4), pp. 456-463. , https://doi.org/10.1164/rccm.201604-0861OC; Augustin, H.G., Koh, G.Y., Thurston, G., Alitalo, K., Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system (2009) Nature Reviews Molecular Cell Biology, 10 (3), pp. 165-177. , https://doi.org/10.1038/nrm2639; Bischof, R.J., Bourke, J.E., Hirst, S.J., Meeusen, E.N.T., Snibson, K.J., Velden, J.V.D., Measurement and impact of remodeling in the lung (2009) Proceedings of the American Thoracic Society, 6 (8), pp. 673-677. , https://doi.org/10.1513/pats.200907-064DP; Borish, L., Culp, J.A., Asthma: A syndrome composed of heterogeneous diseases (2008) Annals of Allergy, Asthma & Immunology, 101 (1), pp. 1-8. , https://doi.org/10.1016/S1081-1206(10)60826-5; Bourdeau, A., Van Slyke, P., Kim, H., Cruz, M., Smith, T., Dumont, D.J., Vasculotide, an Angiopoietin-1 mimetic, ameliorates several features of experimental atopic dermatitis-like disease (2016) BMC Research Notes, 9, p. 289. , https://doi.org/10.1186/s13104-015-1817-1; Campochiaro, P.A., Molecular pathogenesis of retinal and choroidal vascular diseases (2015) Progress in Retinal and Eye Research, 49, pp. 67-81. , https://doi.org/0.1016/j.preteyeres.2015.06.002; Campochiaro, P.A., Peters, K.G., Targeting Tie2 for treatment of diabetic retinopathy and diabetic macular edema (2016) Current Diabetes Reports, 16 (12), p. 126. , https://doi.org/10.1007/s11892-016-0816-5; Cui, X., Chopp, M., Zacharek, A., Cui, Y., Roberts, C., Chen, J., The neurorestorative benefit of GW3965 treatment of stroke in mice (2013) Stroke, 44 (1), pp. 153-161. , https://doi.org/10.1161/STROKEAHA.112.677682; David, S., K{\"u}mpers, P., Van Slyke, P., Parikh, S.M., Mending leaky blood vessels: The angiopoietin-Tie2 pathway in sepsis (2013) Journal of Pharmacology and Experimental Therapeutics, 345 (1), pp. 2-6. , https://doi.org/10.1124/jpet.112.201061; Gamble, J.R., Drew, J., Trezise, L., Underwood, A., Parsons, M., Kasminkas, L., Vadas, M.A., Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions (2000) Circulation Research, 87, pp. 603-607. , https://doi.org/10.1161/01.RES.87.7.603; Ghosh, C.C., David, S., Zhang, R., Berghelli, A., Milam, K., Higgins, S.J., Parikh, S.M., Gene control of tyrosine kinase TIE2 and vascular manifestations of infections (2016) Proceedings of the National Academy of Sciences of the United States of America, 113 (9), pp. 2472-2477. , https://doi.org/10.1073/pnas.1519467113; Kanazawa, H., VEGF, angiopoietin-1 and-2 in bronchial asthma_ new molecular targets in airway angiogenesis and microvascular remodeling (2007) Recent Patents on Inflammation & Allergy Drug Discovery, 1 (1), pp. 1-8. , https://doi.org/10.2174/187221307779815066; Klossek, J.M., Annesi-Maesano, I., Pribil, C., Didier, A., Burden associated with ocular symptoms in allergic rhinitis (2012) International Archives of Allergy and Immunology, 158 (4), pp. 411-417. , https://doi.org/10.1159/000334286; Lee, J.E., Kim, K.R., Rha, K.S., Dhong, H.J., Roh, H.J., Rhee, C.S., Kim, D.Y., Prevalence of ocular symptoms in patients with allergic rhinitis: Korean multicenter study (2013) American Journal of Rhinology & Allergy, 27 (5), pp. e135-e139. , https://doi.org/10.2500/ajra.2013.27.3937; L{\"o}tvall, J., Akdis, C.A., Bacharier, L.B., Bjermer, L., Casale, T.B., Custovic, A., Greenberger, P.A., Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome (2011) Journal of Allergy and Clinical Immunology, 127 (2), pp. 355-360. , https://doi.org/10.1016/j.jaci.2010.11.037; Makinde, T.O., Agrawal, D.K., Increased expression of angiopoietins and Tie2 in the lungs of chronic asthmatic mice (2011) American Journal of Respiratory Cell and Molecular Biology, 44 (3), pp. 384-393. , https://doi.org/0.1165/rccm.2009-0330OC; Pitt, A.D., Smith, A.F., Lindsell, L., Voon, L.W., Rose, P.W., Bron, A.J., Economic and quality-of-life impact of seasonal allergic conjunctivitis in Oxfordshire (2004) Ophthalmic Epidemiology, 11, pp. 17-33. , https://doi.org/10.1076/opep.11.1.17.26437; Rosario, N., Bielory, L., Epidemiology of allergic conjunctivitis (2011) Current Opinion in Allergy and Clinical Immunology, 11 (5), pp. 471-476. , https://doi.org/10.1097/ACI.0b013e32834a9676; R{\"u}big, E., Stypmann, J., Van Slyke, P., Dumont, D.J., Spieker, T., Buscher, K., K{\"u}mpers, P., The synthetic Tie2 agonist peptide vasculotide protects renal vascular barrier function in experimental acute kidney injury (2016) Scientific Reports, 25, p. 22111. , https://doi.org/10.1038/srep22111; Salvato, G., Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects (2001) Thorax, 56 (12), pp. 902-906. , https://doi.org/10.1136/thorax.56.12.902; Shaker, M., Salcone, E., An update on ocular allergy (2016) Current Opinion in Allergy and Clinical Immunology, 16 (5), pp. 505-510. , https://doi.org/10.1097/ACI.0000000000000299; Simoes, D.C., Vassilakopoulos, T., Toumpanakis, D., Petrochilou, K., Roussos, C., Papapetropoulos, A., Angiopoietin-1 protects against airway inflammation and hyperreactivity in asthma (2008) American Journal of Respiratory and Critical Care Medicine, 177 (12), pp. 1314-1321. , https://doi.org/10.1164/rccm.200708-1141OC; Smith, A.F., Pitt, A.D., Rodriguez, A.E., Alio, J.L., Marti, N., Teus, M., Barnes, J.R., The economic and quality of life impact of seasonal allergic conjunctivitis in a Spanish setting (2005) Ophthalmic Epidemiology, 12, pp. 233-242. , https://doi.org/10.1080/09286580590967781; Souma, T., Tompson, S.W., Thomson, B.R., Siggs, O.M., Kizhatil, K., Yamaguchi, S., Young, T.L., Angiopoietin receptor TEK mutations underlie primary congenital glaucoma (2016) The Journal of Clinical Investigation, 126 (7), pp. 2575-2587. , https://doi.org/0.1172/JCI85830; Stull, D.E., Schaefer, M., Crespi, S., Sandor, D.W., Relative strength of relationships of nasal congestion and ocular symptoms with sleep, mood and productivity (2009) Current Medical Research and Opinion, 25, pp. 1785-1792. , https://doi.org/10.1185/03007990903021968; Sugiyama, M.G., Armstrong, S.M., Wang, C., Hwang, D., Leong-Poi, H., Advani, A., Lee, W.L., The Tie2-agonist Vasculotide rescues mice from influenza virus infection (2015) Scientific Reports, 5, p. 11030. , https://doi.org/10.1038/srep11030; Tan, G.S., Cheung, N., Sim{\'o}, R., Cheung, G.C., Wong, T.Y., Diabetic macular oedema (2016) The Lancet Diabetes & Endocrinology, S2213–8587 (16), pp. 30052-30053; Tolgyesi, G., Molnar, V., Semsei, A.F., Kiszel, P., Ungvari, I., Pocza, P., Szalai, C., Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease (2009) International Immunology, 21 (8), pp. 967-975. , https://doi.org/10.1093/intimm/dxp063; Ungvari, I., Hadadi, E., Virag, V., Bikov, A., Nagy, A., Semsei, A.F., Szalai, C., Implication of BIRC5 in asthma pathogenesis (2012) International Immunology, 24 (5), pp. 293-301. , https://doi.org/10.1093/intimm/dxs007",

year = "2018",

doi = "10.1111/iji.12365",

language = "English",

volume = "45",

pages = "102--108",

journal = "International Journal of Immunogenetics",

issn = "1744-3121",

publisher = "John Wiley & Sons Ltd",

number = "3",

}

TY - JOUR

T1 - Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis

AU - Fodor, L.E.

AU - Gézsi, A.

AU - Gál, Z.

AU - Nagy, A.

AU - Kiss, A.

AU - Bikov, A.

AU - Szalai, C.

N1 - Export Date: 31 October 2018 Correspondence Address: Szalai, C.; Department of Genetics, Cell- and Immunobiology, Semmelweis UniversityHungary; email: [email protected] Funding details: NKTH, Nemzeti Kutatási és Technológiai Hivatal Funding details: K81941, OTKA, Országos Tudományos Kutatási Alapprogramok Funding details: K112872, OTKA, Országos Tudományos Kutatási Alapprogramok Funding details: TECH_08-A1/2-2008-0120, NST, National Research Council of Science and Technology Funding details: OTKA, Országos Tudományos Kutatási Alapprogramok Funding text: This study was supported by OTKA (Hungarian Scientific Research Fund): K81941, K112872 (C. Szalai); and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120: (C. Szalai). References: Almoguera, B., Vazquez, L., Mentch, F., Connolly, J., Pacheco, J.A., Sundaresan, A.S., Hakonarson, H., Identification of four novel loci in asthma in European and African American populations (2017) American Journal of Respiratory and Critical Care Medicine, 195 (4), pp. 456-463. , https://doi.org/10.1164/rccm.201604-0861OC; Augustin, H.G., Koh, G.Y., Thurston, G., Alitalo, K., Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system (2009) Nature Reviews Molecular Cell Biology, 10 (3), pp. 165-177. , https://doi.org/10.1038/nrm2639; Bischof, R.J., Bourke, J.E., Hirst, S.J., Meeusen, E.N.T., Snibson, K.J., Velden, J.V.D., Measurement and impact of remodeling in the lung (2009) Proceedings of the American Thoracic Society, 6 (8), pp. 673-677. , https://doi.org/10.1513/pats.200907-064DP; Borish, L., Culp, J.A., Asthma: A syndrome composed of heterogeneous diseases (2008) Annals of Allergy, Asthma & Immunology, 101 (1), pp. 1-8. , https://doi.org/10.1016/S1081-1206(10)60826-5; Bourdeau, A., Van Slyke, P., Kim, H., Cruz, M., Smith, T., Dumont, D.J., Vasculotide, an Angiopoietin-1 mimetic, ameliorates several features of experimental atopic dermatitis-like disease (2016) BMC Research Notes, 9, p. 289. , https://doi.org/10.1186/s13104-015-1817-1; Campochiaro, P.A., Molecular pathogenesis of retinal and choroidal vascular diseases (2015) Progress in Retinal and Eye Research, 49, pp. 67-81. , https://doi.org/0.1016/j.preteyeres.2015.06.002; Campochiaro, P.A., Peters, K.G., Targeting Tie2 for treatment of diabetic retinopathy and diabetic macular edema (2016) Current Diabetes Reports, 16 (12), p. 126. , https://doi.org/10.1007/s11892-016-0816-5; Cui, X., Chopp, M., Zacharek, A., Cui, Y., Roberts, C., Chen, J., The neurorestorative benefit of GW3965 treatment of stroke in mice (2013) Stroke, 44 (1), pp. 153-161. , https://doi.org/10.1161/STROKEAHA.112.677682; David, S., Kümpers, P., Van Slyke, P., Parikh, S.M., Mending leaky blood vessels: The angiopoietin-Tie2 pathway in sepsis (2013) Journal of Pharmacology and Experimental Therapeutics, 345 (1), pp. 2-6. , https://doi.org/10.1124/jpet.112.201061; Gamble, J.R., Drew, J., Trezise, L., Underwood, A., Parsons, M., Kasminkas, L., Vadas, M.A., Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions (2000) Circulation Research, 87, pp. 603-607. , https://doi.org/10.1161/01.RES.87.7.603; Ghosh, C.C., David, S., Zhang, R., Berghelli, A., Milam, K., Higgins, S.J., Parikh, S.M., Gene control of tyrosine kinase TIE2 and vascular manifestations of infections (2016) Proceedings of the National Academy of Sciences of the United States of America, 113 (9), pp. 2472-2477. , https://doi.org/10.1073/pnas.1519467113; Kanazawa, H., VEGF, angiopoietin-1 and-2 in bronchial asthma_ new molecular targets in airway angiogenesis and microvascular remodeling (2007) Recent Patents on Inflammation & Allergy Drug Discovery, 1 (1), pp. 1-8. , https://doi.org/10.2174/187221307779815066; Klossek, J.M., Annesi-Maesano, I., Pribil, C., Didier, A., Burden associated with ocular symptoms in allergic rhinitis (2012) International Archives of Allergy and Immunology, 158 (4), pp. 411-417. , https://doi.org/10.1159/000334286; Lee, J.E., Kim, K.R., Rha, K.S., Dhong, H.J., Roh, H.J., Rhee, C.S., Kim, D.Y., Prevalence of ocular symptoms in patients with allergic rhinitis: Korean multicenter study (2013) American Journal of Rhinology & Allergy, 27 (5), pp. e135-e139. , https://doi.org/10.2500/ajra.2013.27.3937; Lötvall, J., Akdis, C.A., Bacharier, L.B., Bjermer, L., Casale, T.B., Custovic, A., Greenberger, P.A., Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome (2011) Journal of Allergy and Clinical Immunology, 127 (2), pp. 355-360. , https://doi.org/10.1016/j.jaci.2010.11.037; Makinde, T.O., Agrawal, D.K., Increased expression of angiopoietins and Tie2 in the lungs of chronic asthmatic mice (2011) American Journal of Respiratory Cell and Molecular Biology, 44 (3), pp. 384-393. , https://doi.org/0.1165/rccm.2009-0330OC; Pitt, A.D., Smith, A.F., Lindsell, L., Voon, L.W., Rose, P.W., Bron, A.J., Economic and quality-of-life impact of seasonal allergic conjunctivitis in Oxfordshire (2004) Ophthalmic Epidemiology, 11, pp. 17-33. , https://doi.org/10.1076/opep.11.1.17.26437; Rosario, N., Bielory, L., Epidemiology of allergic conjunctivitis (2011) Current Opinion in Allergy and Clinical Immunology, 11 (5), pp. 471-476. , https://doi.org/10.1097/ACI.0b013e32834a9676; Rübig, E., Stypmann, J., Van Slyke, P., Dumont, D.J., Spieker, T., Buscher, K., Kümpers, P., The synthetic Tie2 agonist peptide vasculotide protects renal vascular barrier function in experimental acute kidney injury (2016) Scientific Reports, 25, p. 22111. , https://doi.org/10.1038/srep22111; Salvato, G., Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects (2001) Thorax, 56 (12), pp. 902-906. , https://doi.org/10.1136/thorax.56.12.902; Shaker, M., Salcone, E., An update on ocular allergy (2016) Current Opinion in Allergy and Clinical Immunology, 16 (5), pp. 505-510. , https://doi.org/10.1097/ACI.0000000000000299; Simoes, D.C., Vassilakopoulos, T., Toumpanakis, D., Petrochilou, K., Roussos, C., Papapetropoulos, A., Angiopoietin-1 protects against airway inflammation and hyperreactivity in asthma (2008) American Journal of Respiratory and Critical Care Medicine, 177 (12), pp. 1314-1321. , https://doi.org/10.1164/rccm.200708-1141OC; Smith, A.F., Pitt, A.D., Rodriguez, A.E., Alio, J.L., Marti, N., Teus, M., Barnes, J.R., The economic and quality of life impact of seasonal allergic conjunctivitis in a Spanish setting (2005) Ophthalmic Epidemiology, 12, pp. 233-242. , https://doi.org/10.1080/09286580590967781; Souma, T., Tompson, S.W., Thomson, B.R., Siggs, O.M., Kizhatil, K., Yamaguchi, S., Young, T.L., Angiopoietin receptor TEK mutations underlie primary congenital glaucoma (2016) The Journal of Clinical Investigation, 126 (7), pp. 2575-2587. , https://doi.org/0.1172/JCI85830; Stull, D.E., Schaefer, M., Crespi, S., Sandor, D.W., Relative strength of relationships of nasal congestion and ocular symptoms with sleep, mood and productivity (2009) Current Medical Research and Opinion, 25, pp. 1785-1792. , https://doi.org/10.1185/03007990903021968; Sugiyama, M.G., Armstrong, S.M., Wang, C., Hwang, D., Leong-Poi, H., Advani, A., Lee, W.L., The Tie2-agonist Vasculotide rescues mice from influenza virus infection (2015) Scientific Reports, 5, p. 11030. , https://doi.org/10.1038/srep11030; Tan, G.S., Cheung, N., Simó, R., Cheung, G.C., Wong, T.Y., Diabetic macular oedema (2016) The Lancet Diabetes & Endocrinology, S2213–8587 (16), pp. 30052-30053; Tolgyesi, G., Molnar, V., Semsei, A.F., Kiszel, P., Ungvari, I., Pocza, P., Szalai, C., Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease (2009) International Immunology, 21 (8), pp. 967-975. , https://doi.org/10.1093/intimm/dxp063; Ungvari, I., Hadadi, E., Virag, V., Bikov, A., Nagy, A., Semsei, A.F., Szalai, C., Implication of BIRC5 in asthma pathogenesis (2012) International Immunology, 24 (5), pp. 293-301. , https://doi.org/10.1093/intimm/dxs007

PY - 2018

Y1 - 2018

N2 - 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 important 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 variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated 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 individuals, 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 conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated 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 population (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. © 2018 John Wiley & Sons Ltd

AB - 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 important 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 variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated 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 individuals, 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 conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated 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 population (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. © 2018 John Wiley & Sons Ltd

KW - allergic conjunctivitis

KW - allergy

KW - angiogenesis

KW - asthma

KW - genetics

KW - Tie2

KW - genomic DNA

KW - allele

KW - allergic asthma

KW - Article

KW - child

KW - comorbidity

KW - conjunctivitis

KW - eosinophil count

KW - female

KW - gene

KW - genetic association

KW - genotype

KW - human

KW - major clinical study

KW - male

KW - priority journal

KW - school child

KW - single nucleotide polymorphism

KW - TEK gene

U2 - 10.1111/iji.12365

DO - 10.1111/iji.12365

M3 - Article

SN - 1744-3121

VL - 45

SP - 102

EP - 108

JO - International Journal of Immunogenetics

JF - International Journal of Immunogenetics

IS - 3

ER -

Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis

Abstract

Keywords

UN SDGs

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