Fodor L E, Gézsi A, Gál Z, Nagy A, Kiss A, Bikov A, Szalai C
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Heim Pal Children Hospital, Budapest, Hungary.
Int J Immunogenet. 2018 Jun;45(3):102-108. doi: 10.1111/iji.12365. Epub 2018 Apr 18.
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.
Tie2受体是血管生成中的一个重要参与者。Tie2信使核糖核酸和蛋白质在肺部大量表达，并且相关通路在眼睛的发育和功能中也起着重要作用。Tie2由人类的TEK基因编码。最近，已发现TEK基因的变异与哮喘有关。本研究的目的是调查TEK基因的变异是否会影响儿童哮喘的易感性和/或相关表型，如全球哮喘防治创议（GINA）状态、病毒或运动诱发的哮喘、过敏性哮喘、室内、室外、吸入性过敏、免疫球蛋白E（IgE）和嗜酸性粒细胞水平、过敏性鼻炎和过敏性结膜炎。在1189名无亲缘关系的个体中对TEK基因的三个单核苷酸多态性（SNP，rs3780315、rs581724和rs7876024）进行了基因分型，其中435名是哮喘儿童，754名是健康对照。在320名患者中定义了不同类型的哮喘、过敏和合并症。在320名完全表型化的哮喘患者中，178名（55.6%）也患有过敏性鼻炎，100名（31.3%）患有结膜炎。在鼻炎患者中，98名（55.1%）也患有结膜炎。两名患者患有无鼻炎的结膜炎。基因分型的SNP与哮喘无关联。然而，在哮喘人群中，SNP rs581724以隐性方式与过敏性结膜炎显著相关（p=0.007；比值比（OR）=2.3（1.3 - 4.4））。当将整个人群（哮喘患者和健康对照）纳入计算时，该风险仍然显著（p = 0.003；OR = 2.1（1.3 - 3.6））。与结膜炎风险增加相关的rs581724 SNP的次要等位基因也与Tie2表达降低有关。SNP rs581724与哮喘儿童过敏性结膜炎的发生之间存在显著关联。如果进一步的研究能够证实Tie2通路在过敏性结膜炎中的作用，那么它可能成为该疾病一个潜在的新型治疗靶点。
