Variants in mannose-binding lectin and tumour necrosis factor   affect survival in cystic fibrosis

Buranawuti, Kitti; Boyle, Michael; Cheng, Suzanne; Steiner, Lori; McDougal, Kathryn E.; Fallin, M. Daniele; Merlo, Christian A.; Zeitlin, Pamela L.; Rosenstein, Beryl J.; Mogayzel, Peter J.; Wang, Xinjing; Cutting, Garry R.

doi:10.1136/jmg.2006.046318

Cited by 40 publications

(48 citation statements)

References 29 publications

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“…The distributions of these variants are consistent with other white populations. 12,13,34 Other genotypes of TGFβ1 at the −509 promoter and codon 10 sites were not found to significantly alter the effect of secondhand smoke exposure on lung function (Table 4). Although the T allele at −509 and the C allele on codon 10 frequently travel together, 14,15,17 the number of participants exposed to secondhand smoke in our study carrying TGFβ1 genes with T at −509 and C at codon 10 is too few to permit detailed haplotype analysis to determine whether the T allele at −509, the C allele at codon 10, or the combination of both is responsible for increasing the deleterious effect of secondhand smoke exposure.…”

Section: Gene-environment Interactionsmentioning

confidence: 96%

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Collaco¹,

Vanscoy²,

Bremer³

et al. 2008

JAMA

132

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Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation.Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and ParticipantsRetrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States.Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. ResultsOf 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; PϽ.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-⌬F508 homozygotes (12.8 percentile point decrease; P=.001), TGF␤1−509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGF␤1 codon 10 CC homozygotes (20.3 percentile point decrease; P=.005).Conclusions Any exposure to secondhand smoke adversely affects both crosssectional and longitudinal measures of lung function in individuals with CF. Variations in the gene that causes CF (CFTR) and a CF-modifier gene (TGF␤1) amplify the negative effects of secondhand smoke exposure.

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Section: Gene-environment Interactionsmentioning

confidence: 96%

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Collaco¹,

Vanscoy²,

Bremer³

et al. 2008

JAMA

132

View full text Add to dashboard Cite

show abstract

“…The search for auto-antibodies, as well as other markers of systemic inflammation, could perhaps help us to select patients, possibly paediatric patients, who could benefit from early anti-inflammatory treatments. The study of some modifier genes, such as tumour necrosis factor-a, transforming growth factor-b1 and mannose-binding lectin 2, could also be useful in selecting such patients with exacerbated immune response [31,32].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Lachenal

Nkana²,

Nové-Josserand³

et al. 2009

European Respiratory Journal

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The aim of this study was to determine the prevalence of different auto-antibodies in adult, French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival.The sera of 144 patients were screened for a wide range of antibodies. Clinical, biological and bacteriological characteristics and the cystic fibrosis transmembrane conductance regulator genotype were recorded and progression of lung disease was examined.113 (78.5%) patients displayed one or several auto-antibodies, predominantly immunoglobulin (Ig)A anti-Saccharomyces cerevisiae antibodies (ASCA; 43.7%) and antineutrophil cytoplasmic antibodies (ANCA; 40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, Pseudomonas aeruginosa colonisation, the presence of resistant P. aeruginosa, low forced expiratory volume in 1 s, CF-related liver disease, hypergammaglobulinaemia, male sex and inflammatory syndrome. The presence of ASCA-IgA was correlated with male sex and hypergammaglobulinaemia. 41 patients presented with chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA-IgA.These findings confirm the high frequency of auto-antibodies in CF, particularly BPI-ANCA and ASCA-IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.

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“…One unique strategy for identifying modifiers that may affect survival has been used by Buranawuti and coworkers (47). They took advantage of the fact that a modifier gene polymorphism that causes a significant survival disadvantage should be less prevalent in a cross-sectional sample of an adult population than in a cross-section of a pediatric population.…”

Section: Comparing Polymorphism Prevalence Between Pediatric and Adulmentioning

confidence: 99%

Strategies for Identifying Modifier Genes in Cystic Fibrosis

Boyle

2007

Proceedings of the American Thoracic Society

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Even in patients with cystic fibrosis (CF) with identical CFTR genotypes, there is a wide range in the severity of lung disease, with some individuals facing death or lung transplantation early in life and others demonstrating mild lung disease well into adulthood. Although numerous environmental factors have been identified that influence CF pulmonary phenotype, there is now growing evidence that polymorphic variants in genes besides CFTR play an important role in determining severity of CF lung disease. This article reviews the most recent findings regarding genetic modifiers in CF and also discusses in detail the strategies currently being used to identify novel modifiers of CF pulmonary phenotype. These include single-and multicenter studies, twin and sib studies, microarray approaches, and whole genome association studies.

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Variants in mannose-binding lectin and tumour necrosis factor affect survival in cystic fibrosis

Abstract: TNFalpha-238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis.

Cited by 40 publications

References 29 publications

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Strategies for Identifying Modifier Genes in Cystic Fibrosis

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