Andrea Iorio1,2, Renato Polimanti1, Sara Piacentini1, Giancarlo Maria Liumbruno3, Dario Manfellotto2, Maria Fuciarelli1. 1. Department of Biology, University of Rome 'Tor Vergata', Rome, Italy. 2. Clinical Pathophysiology Center, AFaR - 'San Giovanni Calibita' Fatebenefratelli Hospital, Rome, Italy. 3. Clinical Pathology Department, AFaR - 'San Giovanni Calibita' Fatebenefratelli Hospital, Rome, Italy.
Abstract
BACKGROUND AND AIMS: Allergic rhinitis (AR) is one of the most common respiratory diseases among human populations. Strong evidence suggests that genetic predisposition and environmental factors could contribute to the development of this complex disease. Glutathione S-transferases (GSTs) are biomarkers of inflammation and oxidative stress. These phase II enzymes play a significant role in detoxifying xenobiotic compounds. To analyze the role of GST gene polymorphisms in AR pathogenesis in a case-control population of 103 patients affected by AR and 200 healthy non-allergic subjects. METHODS: We screened genomic DNA extracted from buccal cells for GSTM1 positive/null, GSTP1*I105V (rs1695) and GSTT1 positive/null polymorphisms. The X(2) -test, odds ratio (OR) and logistic regression were used as statistical analyses. RESULTS: Significant differences in null genotype distribution between AR patients (13%) and healthy controls (30%) were found for the GSTT1 null genotype (OR = 0.30, 95% confidence interval = 0.14-0.65; P = 0.001). GSTM1 and GSTP1 polymorphisms did not show any significant results. CONCLUSION: Our data indicated that GSTT1 may be a susceptibility locus for AR. Specifically, the positive/null polymorphism of GSTT1 may be involved in an oxidative stress-related mechanism that may enhance pathogenic pathways related to AR. Moreover, beside GSTT1, this deletion polymorphism affects also another gene potentially related to AR phenotype, LOC391322. This gene belongs to MIF (macrophage migration inhibitory factor) gene family and several studies indicated the role of this gene in several immunology-related phenotypes. Therefore, two different scenarios may explain the observed genetic association.
BACKGROUND AND AIMS: Allergic rhinitis (AR) is one of the most common respiratory diseases among human populations. Strong evidence suggests that genetic predisposition and environmental factors could contribute to the development of this complex disease. Glutathione S-transferases (GSTs) are biomarkers of inflammation and oxidative stress. These phase II enzymes play a significant role in detoxifying xenobiotic compounds. To analyze the role of GST gene polymorphisms in AR pathogenesis in a case-control population of 103 patients affected by AR and 200 healthy non-allergic subjects. METHODS: We screened genomic DNA extracted from buccal cells for GSTM1 positive/null, GSTP1*I105V (rs1695) and GSTT1 positive/null polymorphisms. The X(2) -test, odds ratio (OR) and logistic regression were used as statistical analyses. RESULTS: Significant differences in null genotype distribution between AR patients (13%) and healthy controls (30%) were found for the GSTT1 null genotype (OR = 0.30, 95% confidence interval = 0.14-0.65; P = 0.001). GSTM1 and GSTP1 polymorphisms did not show any significant results. CONCLUSION: Our data indicated that GSTT1 may be a susceptibility locus for AR. Specifically, the positive/null polymorphism of GSTT1 may be involved in an oxidative stress-related mechanism that may enhance pathogenic pathways related to AR. Moreover, beside GSTT1, this deletion polymorphism affects also another gene potentially related to AR phenotype, LOC391322. This gene belongs to MIF (macrophage migration inhibitory factor) gene family and several studies indicated the role of this gene in several immunology-related phenotypes. Therefore, two different scenarios may explain the observed genetic association.
Authors: Francisco J Sánchez-Gómez; Beatriz Díez-Dacal; Elena García-Martín; José A G Agúndez; María A Pajares; Dolores Pérez-Sala Journal: Front Pharmacol Date: 2016-08-04 Impact factor: 5.810