Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

Table 7

Common biochemical abnormalities in redox homeostasis found in asthma and their possible relationship with genes for antioxidant defense enzymes which have been associated with risk of the disease in the present study.

Biochemical abnormalities in asthmatics [references]	ADE gene related with the abnormality	Allergic asthma		Nonallergic asthma
		Men	Women	Men	Women
Diminished capacity of glutathione peroxidases and catalase in detoxification of hydrogen peroxide [22, 38–43].	GPX1	+ + +	+ +	+ +	+ +
	GPX2	+ +	−		+ + +
	GPX3	−	−	+ +	−
	GPX4	−	+	−	−
	CAT	+ + +	−	+ +	−
An enhanced production of ROS/hydrogen peroxide/superoxide anion radicals [22, 44–50].	CYBA (640A>G)	−	+	−	−
	CYBA (−930A>G)	−	−	+ + +	−
Perturbations in glutathione (GSH) homeostasis [41, 48, 50–52].	GSR	+ +	−	+ + +	−
	GCLM	+ +	−	+ + +	−
Increased EPHX1 activity, increased production of xenobiotics-generated epoxides, trans-dihydrodiols and reactive semiquinones resulting in ROS generation [53, 54].	EPHX1	+ +	+ + +	+ +	+ + +

The number of pluses means a degree of the relationship between the gene and asthma risk. These measures reflect how many times a particular gene showed the link with asthma risk through the three methods used for evaluation of gene-gene interactions in the present study, namely, set association approach (SAA), multifactor dimensionality reduction (MDR) method, and post hoc association analysis of two-locus genotype combinations (AAGC): + + + means that the link was found thrice (i.e., using SAA, MDR, and AAGC methods); + + means that the link was found twice (i.e., using SAA or MDR and AAGC methods); + means that the link was found once by AAGC method. Associations are stratified by asthma type and gender.