MBL2 polymorphisms screening in a regional Italian CF Center

Trevisiol, Chiara; Boniotto, Michele; Giglio, L.; Poli, Furio; Morgutti, Marcello; Crovella, Sérgio

doi:10.1016/j.jcf.2005.04.001

Cited by 17 publications

(25 citation statements)

References 11 publications

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“…The time-to-event analysis showed that MBL2 deficiency was strongly associated with earlier acquisition of P. aeruginosa in young children with CF (P = 0.0003; Figure 2). This modulatory effect most likely reflects the critical role of MBL2 in the first defense against bacterial colonization (16) and supports the similar but less significant effect previously observed in a small Italian CF patient cohort (42). However, it should be also noted that although MBL2 deficiency has been implicated in many studies as contributing to higher susceptibility to infections, there are also data suggesting the opposite (43).…”

Section: Discussionsupporting

confidence: 81%

Complex two-gene modulation of lung disease severity in children with cystic fibrosis

Dorfman¹,

Sandford²,

Taylor³

et al. 2008

J. Clin. Invest.

134

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Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.

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Section: Discussionsupporting

confidence: 81%

Complex two-gene modulation of lung disease severity in children with cystic fibrosis

Dorfman¹,

Sandford²,

Taylor³

et al. 2008

J. Clin. Invest.

134

View full text Add to dashboard Cite

show abstract

“…Chronic Pa colonization is age-dependent and the majority of cystic fibrosis patients become colonized over time. Age at onset of Pa colonization is a more useful outcome parameter as earlier age correlates with poor prognosis [6,30,4,7,8,31].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients

et al. 2012

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“…a.) (Table 2) (Trevisiol et al 2005;Dorfman et al 2008;McDougal et al 2010). Because severity of lung disease, Ps.…”

Section: Lung Diseasementioning

confidence: 99%

“…MBL2 is biologically plausible, because of its role in innate immunity and the predilection of MBL2 deficient patients to bacterial and viral infection. Six studies involving .2000 CF patients have shown that MBL-deficient genotypes (OO or AO) are associated with worse lung function (Table 2) (Gabolde et al 1999;Garred et al 1999;Davies et al 2004;Yarden et al 2004;Trevisiol et al 2005;Dorfman et al 2008), and three studies reported earlier age of infection with Pseudomonas aeruginosa (Ps. a.)…”

Section: Lung Diseasementioning

confidence: 99%