METABOLIC GENE POLYMORPHISMS ASSOCIATED WITH ATOPIC BRONCHIAL ASTHMA
Ivaschenko TE1, Sideleva OG1, Zelenina LA2, Antonova EA2, Ostankova JV1, Aseev MV1, Baranov VS1
*Corresponding Author: Professor Dr. Vladislav S. Baranov, Ott’s Institute of Obstetrics/Gynecology, Russian Academy of Medical Sciences, Mendeleevskaya line 3, 199034 St. Petersburg, Russia; Tel/Fax: +07(812) 3280487 E-mail: baranov@vb2475.spb.edu
page: 23

INTRODUCTION

The prevalence of asthma, allergic rhinitis and atopic dermatitis has dramatically increased over the past few decades. These atopy-related disease are the common chronic disorders of childhood. Asthma is a complex polygenic disorder, most probably caused by an interaction of multiple disease susceptibility genes with poorly identified environmental factors. The search for the genes participating in the origin and progression of asthma has already led to the identification of several loci on chromosomes 5, 11 and 12 [1-3]. The number of genes involved in this complex disorder have not yet been fully determined. The severity of the disease phenotype varies between individuals, and it is likely that some unique combinations of certain polymorphisms of particular genes constitute the inherited background of asthma severity.

Asthma is characterized by airway inflammation, a critical component of which is oxidative stress. Oxidative stress, with the formation of reaction oxygen species (ROS), is a key component of inflammation [4,5]. Although host antioxidant defenses should detoxify ROS, individuals differ in their ability to deal with an oxidant burden, and such differences are, in part, genetically determined [5]. Inability to detoxify ROS should perpetuate the inflammatory process, activate broncho-constrictor mechanisms, and potentiate asthmatic symptoms.

The high population prevalence of asthma substantiated the investigation on possible participation of the detoxification system genes such as mEPHX and NAT2 in the pathogenesis of this disease [6,7]. It was shown that a polymorphism of the GSTP1 gene, responsible for the enzyme of phase II of detoxification, is strongly associated with asthma, and provides an alternative explanation for the genetic linkage of atopy with chromosome locus 11q13 [8].

We hypothesized that the GST super-gene family is an attractive candidate, associated with asthma. The enzymes encoded by the members of the mu, theta, and pi class GST families can utilize as substrates a wide variety of products of oxidative stress, and are thus critical in the protection of cells from ROS [9].

The enzymes encoded by different GST gene classes preferentially metabolize different ROS products. For example, quinone metabolites of catecholamines (dopa­chrome) are utilized by mu GST but not by GSTP1 or GSTT1. Mu and theta, but not pi, GST genes demonstrate preferential activity against phospholipid hydroperoxide.

These GST genes may also influence the synthesis of eicosanoids (critical mediators in the asthmatic response) via modulation of ROS level [9]. Furthermore, the products are essential for mobilization of arachidonic acid, with subsequent production of pro-inflammatory eicosanoids.

So far, common allelic variants have been identified in the mu (GSTM10/0), the theta (GSTT10/0), and the pi (GSTP1 B, GSTP1 C) class genes. We have examined the hypothesis that polymorphisms of the GSTM1, GSTT1, and GSTP1 genes are associated with asthma.




Number 26
VOL. 26(1), 2023
Number 25
VOL. 25(2), 2022
Number 25
VOL. 25 (1), 2022
Number 24
VOL. 24(2), 2021
Number 24
VOL. 24(1), 2021
Number 23
VOL. 23(2), 2020
Number 22
VOL. 22(2), 2019
Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006