Associação entre os polimorfismos dos genes MBL2, TGF-β1 e CD14 com a gravidade da doença pulmonar na fibrose cística

Faria, Elisângela Jacinto de; Faria, Isabel; Ribeiro, José Dirceu; Ribeiro, Antônio Fernando; Hessel, Gabriel; Bertuzzo, Carmen Sílvia

doi:10.1590/s1806-37132009000400007

Cited by 21 publications

(9 citation statements)

References 24 publications

(27 reference statements)

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“…Essa mutação é responsável por 66% a 80% dos fenótipos de FC em todo o mundo (BORTHWICK, 2011;SARAIVA-PEREIRA et al, 2011;PEREIRA et al, 2012), sendo também a mutação mais frequente na população caucasiana com a FC (CARAKUSHANSKY, 2001;FARIA et al, 2009;OTTO, 2013 A maioria das quase 2.000 mutações restantes do gene cftr são raras (MARSON et al, 2015), sendo quatro mutações com frequência alélica acima de 1% entre os indivíduos afetados: p.Gly542X,.Gly551Asp, p.Asn1303Lys e p.Trp1282X em estatística mundial (SARAIVA-PEREIRA et al, 2011). A frequência e a distribuição das mutações no cftr variam de acordo com a origem étnica e a localização geográfica dos pacientes com FC (SINGH et al, 2015).…”

Section: Genéticaunclassified

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Aspectos Genéticos E Clínicos Da Fibrose Cística

Santos¹,

Vinhal²,

Santo³

et al. 2017

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Section: Genéticaunclassified

“…Esse gene codifica a proteína CFTR (Cystic Fibrosis Transmembrane Condutance Regulator, do inglês Reguladora de Condutância Transmembrana de Fibrose Cística) (YOUNG, 2007;FARIA et al, 2009).…”

Section: Introductionunclassified

Aspectos Genéticos E Clínicos Da Fibrose Cística

Santos¹,

Vinhal²,

Santo³

et al. 2017

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“…In fact, a study by Davies et al (2004) found no association between pulmonary function and MBL genotype in children. Despite replications, not all studies have detected associations between MBL alleles and lung disease severity (Carlsson et al, 2005; Drumm et al, 2005; Faria et al, 2009; McDougal et al, 2010). …”

Section: Associating Genes and Insight Into Their Modifying Mechanismsmentioning

confidence: 99%

“…The same study, by Drumm et al found that the -509 T allele also associated with a severe pulmonary phenotype, which is the same adverse effect seen in asthma populations. There have been several attempts to resolve these conflicting data (Arkwright et al, 2000, 2003; Drumm et al, 2005; Brazova et al, 2006; Buranawuti et al, 2007; Bremer et al, 2008; Corvol et al, 2008; Faria et al, 2009), but only one study has used a relatively large cohort to accommodate the statistical power needed. It found that a haplotype of a 3′ C allele (rs8179181), -509 C, and codon 10 T associated with improved lung function to a greater degree than any SNP alone (Bremer et al, 2008).…”

Section: Associating Genes and Insight Into Their Modifying Mechanismsmentioning

confidence: 99%

Genetic Influences on Cystic Fibrosis Lung Disease Severity

Weiler¹,

Drumm²

2013

Front. Pharmacol.

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Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development.

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“…In our group, as previously published, multiple genes are associated with CF clinical severity, including Transforming growth factor beta 1 ( TGF - β1 ) [11], Glutathione S-transferase Mu 1 ( GSTM1 ), Glutathione S-transferase Theta 1 ( GSTT1 ) [12], Angiotensin-converting enzyme ( ACE ) [13] and Beta-2-Adrenergic Receptor ( ADBR2 ) [14] genes as possibly modifier genes. In the same population the mannose-binding lectin (protein C) 2 ( MBL2 ) and monocyte differentiation antigen CD14 ( CD14 ) genes were not associated with the CF clinical severity [11]. …”

Section: Introductionmentioning

confidence: 99%

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis

et al. 2013

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BackgroundCystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.MethodA total of 180 CF’s patients were included in this study, which investigated polymorphisms in GCLC and GST genes (GCLC -129C>T and -3506A>G; GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G) by PCR and PCR-RFLP associating to clinical variables of CF severity, including variables of sex, clinical scores [Shwachman-Kulczycki, Kanga e Bhalla (BS)], body mass index, patient age, age for diagnosis, first clinical symptoms, first colonization by Pseudomonas aeruginosa, sputum’s microorganisms, hemoglobin oxygen saturation in the blood, spirometry and comorbidities. The CFTR genotype was investigated in all patients, and the genetic interaction was performed using MDR2.0 and MDRPT0.4.7 software.ResultsThe analysis of multiple genes in metabolic pathways in diseases with variable clinical expression, as CF disease, enables understanding of phenotypic diversity. Our data show evidence of interaction between the GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G polymorphism with CFTR gene mutation classes, and BS (Balance testing accuracy= 0.6824, p= 0.008), which measures the commitment of bronchopulmonary segments by tomography.ConclusionPolymorphisms in genes associated with metabolism of GSH act on the CF’s severity.

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Associação entre os polimorfismos dos genes MBL2, TGF-β1 e CD14 com a gravidade da doença pulmonar na fibrose cística

Cited by 21 publications

References 24 publications

Aspectos Genéticos E Clínicos Da Fibrose Cística

Aspectos Genéticos E Clínicos Da Fibrose Cística

Genetic Influences on Cystic Fibrosis Lung Disease Severity

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis

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