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

被引:31
作者
Buranawuti, Kitti
Boyle, Michael P.
Cheng, Suzanne
Steiner, Lori L.
McDougal, Kathryn
Fallin, M. Daniele
Merlo, Christian
Zeitlin, Pamela L.
Rosenstein, Beryl J.
Mogayzel, Peter J., Jr.
Wang, Xinjing
Cutting, Garry R.
机构
[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA
[3] Roche Mol Syst Inc, Dept Human Genet, Alameda, CA USA
[4] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[5] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
关键词
D O I
10.1136/jmg.2006.046318
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 alpha (TNF alpha), transforming growth factor beta 1 (TGF beta 1) or mannose-binding lectin (MBL2)) differed among patients with cystic fibrosis grouped according to age and survival status. Methods: Genotypes of four variants (TNF alpha-238, TNF alpha-308, TGF beta 1-509 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 nonsurviving 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 TNF alpha-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 ( TNF alpha-238 G/G vs G/A; p = 0.0015 and MBL2: A/A vs O/O; p = 0.009). The hazard ratio for TNF alpha-238 G/ G vs G/A was 0.25 (95% Cl 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: TNF alpha-238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis.
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页码:209 / 214
页数:6
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