Beta-2-adrenergic receptor polymorphisms in cystic fibrosis

Steagall, Wendy K.; Barrow, Bethany J.; Glasgow, Connie G.; Mendoza, Jennifer Woo; Ehrmantraut, Mary; Lin, Jing‐Ping; Insel, Paul A.; Moss, Joel

doi:10.1097/fpc.0b013e3280119349

Cited by 13 publications

(15 citation statements)

References 38 publications

(92 reference statements)

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“…Published studies have examined mostly immune or inflammatory genes, including ACE [19,20], ADRβ2 [20–23], ATB 0 [24], CAPN10 [25], ClCN2 [26], DEFβ4 [27], ENaC [28], FcβRII [29], GCLC [30], GSTM1 [20,31–35], GSTM3 [34], GSTP1 [20,33–35], GSTT1 [34], HFE [36,37], HLA-I [38], HLA-II [38–41], HLA-III [38], HSP70 [39], IFN-γ [19], IL1-β [39], IL6 [25], IL10 [19,20,42], IL18 [25], KCNJ11 [25], MBL2 [20,43–52,53 •• ], MIF [54], NOS1 [55–57], NOS3 [20,58], MASP-2 [48,51], PPARβ [25], SERPINA1 [20,59–67], SERPINA3 [68], SFTPA1 [50], SFTPA2 [50], TLR4 [69], TGFB1 [19,20,52,53 ββ ,67,70–72 •• ,73 •• ], TNFα [19,20,25,32,52,74–76], TNFα -receptor [28], and TNFβ [39]. …”

Section: Candidate Gene Studiesmentioning

confidence: 99%

“…In regard to clinical phenotypes, only effects on lung disease were investigated by more than one study. Three studies [20,22,23] saw no association of lung disease with the codon 16 or codon 27 polymorphisms, although one study [21] reported worse function and decline in individuals who carried a Gly/Gly or Arg/Gly genotype at codon 16 or a Glu/Glu or Gln/Glu genotype at codon 27.…”

Section: Candidate Gene Studiesmentioning

confidence: 99%

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Update on gene modifiers in cystic fibrosis

Collaco¹,

Cutting

2008

Current Opinion in Pulmonary Medicine

119

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Purpose of review Cystic fibrosis (CF) is a common, life-limiting monogenic disease, which typically manifests as progressive bronchiectasis, exocrine pancreatic dysfunction, and recurrent sinopulmonary infections. Although the gene responsible for CF (CFTR) was described in 1989, it has become increasingly evident that modifier genes and environmental factors play substantial roles in determining the severity of disease, particularly lung disease. Identifying these factors is crucial in devising therapies and other interventions to decrease the morbidity and mortality associated with this disorder. Recent findings Although many genes have been proposed as potential modifiers of CF, only a handful have withstood the test of replication. Several of the replicated findings reveal that genes affecting inflammation and infection response play a key role in modifying CF lung disease severity. Interactions between CFTR genotype, modifier genes, and environmental factors have been documented to influence lung function measures and infection status in CF patients. Summary Several genes have been demonstrated to affect disease severity in CF. Furthermore, it is likely that gene–gene and gene–environment interactions can explain a substantial portion of the variation of lung disease. Ongoing genome-wide studies are likely to identify novel genetic modifiers. Continued exploration of the role of genetic and nongenetic modifiers of CF is likely to yield new options for combating this debilitating disease.

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Section: Candidate Gene Studiesmentioning

confidence: 99%

Section: Candidate Gene Studiesmentioning

confidence: 99%

Update on gene modifiers in cystic fibrosis

Collaco¹,

Cutting

2008

Current Opinion in Pulmonary Medicine

119

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“…The effectiveness of asthma’s response to the BD is dependent on polymorphisms in ADRB2 gene . In contrast, with CF, little is known about the response to the BD and the CF´s severity in association with the different polymorphisms in ADRB2 gene [17-19]. Although previous studies had showed an association between bronchodilator response and the polymorphisms in the ADRB2 gene, these studies did not take into account secondary clinical variables that can provide extra information about the mechanism associated with action of the ADRB2 protein.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis

et al. 2012

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BackgroundThe most common cystic fibrosis (CF) manifestation is the progressive chronic obstructive pulmonary disease caused by deficiency, dysfunction, or absence of the CFTR (Cystic Fibrosis Transmembrane Regulator) protein on the apical surface of the cells in the respiratory tract. The use of bronchodilators (BD), and inhaled corticosteroids (IC) have been suggested for the management of airway inflammation in CF. The effectiveness of BD and IC have been verified, proven in laboratory and in the clinical treatment for asthma patients. However, in CF, the effectiveness of these drugs is controversial. The extent of asthma’s response to BD depends on the presence of polymorphisms in the ADRB2 gene. In contrast, in CF, little is known about the response to the BD and the association of CF´s severity with the different polymorphisms in ADRB2 gene. In this context, our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene are associated with severity and with the bronchodilator response in CF patients.MethodCross-sectional study of 122 CF patients subjected to analysis of mutations in the CFTR gene, polymorphisms in ADRB2 gene, along with clinical and laboratorial characteristics of severity.ResultThe Arg16Gly polymorphism in ADRB2 gene was associated with pancreatic insufficiency(p:0.009), Bhalla score(p:0.039), forced expiratory volume in the first second[FEV1(%)](p:0.003), forced expiratory flow between 25 and 75% of the forced vital capacity-FVC[FEF25-75(%)](p:0.008) and lower age at the first isolation of the Pseudomonas aeruginosa(p:0.012). The response to the BD spirometry was associated with clinical severity markers, FEV1(%)(p:0.011) and FEF25-75(%)(p:0.019), for the Arg16Gly polymorphism in the ADRB2 gene. The haplotype analysis showed association with the FEV1/FVC marker from the spirometry test, before and after using the BD, with higher values in the group with Gly/Gly and Glu/Glu, respectively, for the Arg16Gly and Gln27Glu polymorphisms. The analysis by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly was respondent by 17.35% and Gln27Glu by 6.8% in variation found.ConclusionThere was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.

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“…The c.46AϾG and the c.79CϾG variants have also been associated with hypertension, 21 heart failure 22,23 obesity and metabolic alterations, 24,25 dislipoproteinemia, and type II diabetes, 26 in predicting survival associated with ␤-blocker therapy after acute coronary syndrome 27 and cystic fibrosis. 28 These findings have generated considerable interest in the development of molecular assays to detect ADRB2 allelic variants. These assays have relied on preliminary amplification of ADRB2 sequences by polymerase chain reaction (PCR) and subsequent identification by a variety of methods such as direct sequencing, 29 allele-specific oligonucleotide hybridization, 10,30 and allele-specific multiplex PCR with agarose gel detection.…”

mentioning

confidence: 99%

A Simple and Rapid Genotyping Assay for Simultaneous Detection of Two ADRB2 Allelic Variants Using Fluorescence Resonance Energy Transfer Probes and Melting Curve Analysis

Sabato

Irani

Bukaveckas

et al. 2008

The Journal of Molecular Diagnostics

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Allelic variants at codons 16 and 27 of the ␤ 2 -adrenergic receptor gene (ADRB2) have shown clinical and pharmacological implications in asthma , hypertension , ischemic heart failure , diabetes , obesity, and cystic fibrosis. We have developed a simultaneous genotyping assay for the c.46A>G and c.79C>G allelic variants using hybridization probes and melting curve analysis. The assay was optimized on a panel of 30 DNA samples of known ADRB2 genotype as determined by sequencing with 100% concordance between the two techniques. Melting temperature (Tm) ranges for the different genotypes were obtained using data from three independent experiments. Single peaks for p.Arg16Arg (Tm ‫؍‬ 57.76°C ؎ 0.10°C) and p.Gly16Gly (Tm ‫؍‬ 66.73°C ؎ 0.18°C) and two melting peaks for p.Arg16Gly were obtained. Similarly , single peaks for p.Gln27Gln

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Beta-2-adrenergic receptor polymorphisms in cystic fibrosis

Cited by 13 publications

References 38 publications

Update on gene modifiers in cystic fibrosis

Update on gene modifiers in cystic fibrosis

Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis

A Simple and Rapid Genotyping Assay for Simultaneous Detection of Two ADRB2 Allelic Variants Using Fluorescence Resonance Energy Transfer Probes and Melting Curve Analysis

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