Delivered by Ingenta to: University of Virginia Claude Moore Health Sciences Library IP: 79.110.17.86 On: Sun, 19 Jun 2016 08:40:34 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm Assessment for microsatellite DNA instability in nasal cytology samples of patients with allergic rhinitis Alexander D. Karatzanis, M.D.,* Katerina D. Samara, M.D.,# Maria Zervou, M.Sc.,# Eleni Tzortzaki, M.D.,# Emmanuel S. Helidonis, M.D.,* Nikolaos Siafakas, M.D.,# and George A. Velegrakis, M.D.* (Greece) ABSTRACT Background: Genetic alterations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), have been described in both malignant and benign diseases. Previous studies have successfully detected such alterations in sputum samples of patients with bronchial asthma (BA). The aim of this study was to assess the presence of MSI and/or LOH in nasal cytology samples of patients with allergic rhinitis (AR). Methods: Nasal brush samples and peripheral blood from 20 patients with AR were analyzed. DNA was extracted and analyzed for MSI and LOH using the following microsatellite markers: D16S289, D4S2394, D4S1651, DXS8039, D3S3606, and D2S2113, harboring potential susceptibility genes for AR and atopy. Microsatellite analysis was performed also in eight control subjects. Results: No MSI and/or LOH were noted in either the AR or the control group. Conclusion: Although MSI and LOH are detectable phenomena in sputum samples of patients with BA, this seems not to be the case for nasal cytology samples of patients with AR. Additional studies are needed, using a larger number of polymorphic markers, to assess if such a difference exists among two diseases otherwise very closely related. (Am J Rhinol 21, 236 –240, 2007; doi: 10.2500/ajr.2007.21.2956) Key words: Allergy rhinitis, DNA markers, genetics, loss of heterozygosity, microsatellite instability A llergic rhinitis (AR) is an IgE-mediated inflammation of the nose induced after allergen exposure. Symptoms of AR include rhinorrhea, nasal obstruction, nasal itching, and sneezing, which are reversible spontaneously or with treat- ment. 1 AR is the most common among atopic diseases and represents a global health problem. It affects up to 25% of adults and perhaps 40% of children in Western societies. The associated socioeconomic cost is very significant because AR affects school performance, socialization, and work pro- ductivity. 2–4 Despite recognizing AR as a global health problem, many aspects regarding the pathophysiology and natural history of the disease still have not been clarified. Moreover, although a genetic component in AR and other allergic diseases has been shown, no genes have been found as clearly predisposing individuals to AR. 1 Nevertheless, many genes are candidates to explain the genetic component of AR and atopy. 5–7 AR and bronchial asthma (BA) are two entities often coex- isting. In fact, during recent years the concept “one airway, one disease” has been proposed. It is now well understood that the epidemiological association between BA and AR is very strong. In addition, the two entities seem to share com- mon genetic and environmental risk factors, while the immu- nopathology of rhinitis and asthma are virtually the same. All this new knowledge about the pathophysiological mecha- nisms of allergic inflammation of the human airways has resulted in better therapeutic strategies. 1,8–11 Deoxyribonucleic acid (DNA) microsatellites (MSs) are highly polymorphic markers used for genome mapping in many organisms including humans. 12 Loss of heterozygos- ity (LOH) and MS instability (MSI) are genetic alterations that have been reported initially in a number of human malignancies. 13–15 During recent years, such phenomena also have been detected in various benign diseases, includ- ing actinic keratosis, pterygium, atherosclerosis, chronic obstructive pulmonary disease, and asthma. 16–19 Therefore, MSI and LOH have been proposed as important genetic screening tools. 12 Because the prementioned genetic alter- ations have been detected successfully in sputum cells of patients with BA, 16 and given the very close relationship between AR and BA, the aim of this study was to investi- gate the presence of LOH and/or MI in nasal cytology samples of patients with AR. PATIENTS AND METHODS A total of 20 patients with AR, aged 21–62 years, were studied. Only patients with clinical AR and elevated specific IgE against at least one of the tested allergens were included. AR was diagnosed according to standard criteria. 20 The spe- cific IgE measurements, with the use of C.A.R.L.A. (Capture Assay Radim Liquid Allergen; RADIM SpA, Rome, Italy) RAST, were considered to be elevated when 0.5 IU/mL (class 1 or greater). Specific IgE measurements were deter- mined for the following allergens: dust mites (Dermatopha- goides pteronyssinus and Dermatophagoides farinae), cat and dog epithelia, olive, Aspergillus fumigatus, Alternaria alternata, Pa- rietaria judaica, and ragweed. In addition, a control group was studied, consisting of eight individuals with negative history and clinical examination for AR, plus negative specific IgE From the Departments of *Otorhinolaryngology, Head and Neck Surgery, and #Tho- racic Medicine, Medical School, University of Crete, Heraklion, Crete, Greece Supported by an unrestricted research grant from Hellenic Ministery of Education, “The Pythagoras project 2005” Address correspondence and reprint requests to Alexander D. Karatzanis, M.D., Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Medical School, University of Crete, Heraklion 71110, Crete, Greece E-mail address: akaratzanis@yahoo.com Copyright © 2007, OceanSide Publications, Inc., U.S.A. 236 March–April 2007, Vol. 21, No. 2