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

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

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Background: Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality. Objective: To determine if the genotype distribution of variants in three putative cystic fibrosis modifier genes (tumour necrosis factor α (TNFα), transforming growth factor β1 (TGFβ1) or mannose-binding lectin (MBL2)) differed among patients with cystic fibrosis grouped according to age and survival status. Methods: Genotypes of four variants (TNFα-238, TNFα-308, TGFβ1-509 and MBL2 O) were determined in three groups of Caucasians from a single medical centre: 101 children with cystic fibrosis (aged <17 years; mean age 9.4 years), 115 adults with cystic fibrosis (aged ≥17 years; mean age 30.8 years) and 38 non-surviving adults with cystic fibrosis (21 deceased and 17 lung transplant after 17 years of age). Genotypes of 127 healthy Caucasians in the same geographical region were used as controls. Kaplan-Meier and Cox hazard regression were used to evaluate the genotype effect on cumulative survival. Results: Genotype frequencies among adults and children with cystic fibrosis differed for TNFα-238 (G/G vs G/A; p = 0.022) and MBL2 (A/A vs O/O; p = 0.016). When adults with cystic fibrosis were compared to non-surviving adults with cystic fibrosis, genotype frequencies of both genes differed (TNFα-238 G/G vs G/A; p = 0.0015 and MBL2: A/A vs O/O; p = 0.009). The hazard ratio for TNFα-238 G/G vs G/A was 0.25 (95% CI 0.06 to 1.0, p = 0.04) and for MBL2 O/O vs A/A or A/O was 2.5 (95% CI 1.3 to 4.9, p = 0.007). Conclusions: TNFα-238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalJournal of medical genetics
Issue number3
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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