Glucocorticoid receptor gene polymorphisms and potential association to chronic obstructive pulmonary disease susceptibility and severity

Abstract

ObjectiveAs chronic obstructive pulmonary disease (COPD) is known for poor glucocorticoid (GC) response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR) gene might predispose for COPD and/or disease severity.Materials and methodsThree out of about 50 of the most abundant receptor GR gene polymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV) and 106 age matched healthy subjects (mean FEV1 101.8% predicted). These were genotyped: a) for the N363S (Exon 2; 1220 A > G (I)); b) the BCLI restriction fragment length polymorphism (Intron 2; 647 C > G (II)); and c) the ER2223EK (Exon 2; 198, 200 G > A (III)), using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood.ResultsGenotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms. N363S was found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4%) group (controls 60.4%). ER2223EK lacks in any of the study subjects. Further, SNPs did not correlate with COPD severity stage (GOLD), exacerbation rates, and clinical course.ConclusionCOPD is not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed only these 3 receptor gene polymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence.

Corticotropin-releasing hormone receptor-1 and 2 activity produces divergent resistance against stress-induced pulmonary Streptococcus pneumoniae infection

“…type or quality of the stressor) (Cohen et al, 1993; Gonzalez-Gay et al, 2003; Ziaian et al, 2006; Gonzales et al, 2008; Turyk et al, 2008; Wang et al, 2008; Bailey et al, 2009; Kimura et al, 2009; Schwabe et al, 2009; Deshmukh et al, 2010; Heffner, 2011). Elevations in glucocorticoids for example, have been shown to suppress cell-mediated immune responses resulting in susceptibility to infectious and non-infectious disease states (Ferrari, 2003; Schwabe et al, 2009; Solodushko et al, 2009; Elftman et al, 2010; Smets et al, 2010; Sommershof et al, 2011). In contrast, stress-induced activation of sympathetic nervous system pathways has been shown to provoke heighted immune responses, resulting in immune-mediated pathogenesis (Chen and Miller, 2007; Bhowmick et al, 2009; Meyer et al, 2009; Perez et al, 2009).…”

The polymorphism -2548 G/A in leptin and severity of Chronic Obstructive Pulmonary Disease

“…The GSTP1 I105V polymorphism was protective for COPD in Asian populations only. However, a number of other studies have found the opposite results, COPD was not linked to gene polymorphisms N363S, BCLI‐RFLP, and ER2223EK (Schwabe et al. , 2009).…”

“…The GSTP1 I105V polymorphism was protective for COPD in Asian populations only. However, a number of other studies have found the opposite results, COPD was not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK (Schwabe et al, 2009). It is known that leptin is a vasoactive protein that structurally belongs to the long-chain helical cytokine family and is influenced by proinflammatory cytokines.…”

Lung Development Genes and Adult Lung Function

“…SOX9 was associated with adult FEV 1 in a study that included SNP by smoking interaction ( 33 ). NR3C1 was previously identified in a GWAS of spirometrically defined COPD ( 34 ); recently, an intergenic variant annotated to NR3C1 ( NR3C1/ARHGAP26 locus) was also associated with FEV 1 /FVC in a methodological study incorporating functional genomics data to increase power in the GWAS ( 35 ). Interestingly, two additional genes were previously associated with asthma-related phenotypes, RUNX1 with pediatric asthma ( 36 ) and IgE concentrations ( 37 ) in two candidate-gene studies, and ITGB5 with airway hyperresponsiveness in individuals with asthma in a GWAS ( 38 ).…”