Modifier genes and variation in cystic fibrosis

Respiratory Research

Mitchell L Drumm¹ 

[1] Department of Pediatrics, Department of Genetics, and the Institute for Human Genetics, Case Western Reserve University, Cleveland, Ohio, USA

关键词: pulmonary function;    ion transport;    inflammation;    infection;    genetic variation;   

Others  :  1227454
DOI  :  10.1186/rr47

 received in 2001-01-15, accepted in 2001-02-27,  发布年份 2001

【 摘 要 】

The availability of molecular tools to carry out genotyping has led to a flurry of association studies between specific genes and clinical indices of disease or disease susceptibility. Human studies, for the most part, have a limited number of subjects available, precluding whole genome types of approaches. 'Candidate gene' strategies have consequently become widespread, probably in part due to the inherent similarity to clinical association studies. Such studies in cystic fibrosis have found tantalizing results in genes involved in infection and inflammation, but many other relevant pathways remain untapped. Genome scanning approaches may eventually uncover genes not currently recognized as important to cystic fibrosis. In the meantime, while thousands of polymorphisms are cataloged and other genomic resources become more available, the number of association studies with candidate genes will no doubt increase. To make sense of these studies, the choice of gene and phenotype must be carefully considered.

【 授权许可】

   
2001 BioMed Central Ltd

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Rozmahel R, Wilschanski M, Matin A, Plyte S, Oliver M, Auerbach W, Moore A, Forstner J, Durie P, Nadeau J, Bear C, Tsui LC: Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet 1996, 12:280-287.
• [2]Zielenski J, Corey M, Rozmahel R, Markiewicz D, Aznarez I, Casals T, Larriba S, Mercier B, Cutting GR, Krebsova A, Macek M Jr, Langfelder-Schwind E, Marshall BC, DeCelie-Germana J, Claustres M, Palacio A, Bal J, Nowakowska A, Ferec C, Estivill X, Durie P, Tsui LC: Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nat Genet 1999, 22:128-129.
• [3]Davis PB, Drumm M, Konstan MW: Cystic fibrosis. Am J Respir Crit Care Med 1996, 154:1229-1256.
• [4]Robinson W, Waltz DA: FEV(1) as a guide to lung transplant referral in young patients with cystic fibrosis. Pediatr Pulmonol 2000, 30:198-202.
• [5]Corey M, Edwards L, Levison H, Knowles M: Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis. J Pediatr 1997, 131:809-814.
• [6]Garred P, Pressler T, Madsen HO, Frederiksen B, Svejgaard A, Hoiby N, Schwartz M, Koch C: Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest 1999, 104:431-437.
• [7]Gabolde M, Guilloud-Bataille M, Feingold J, Besmond C: Association of variant alleles of mannose binding lectin with severity of pulmonary disease in cystic fibrosis: cohort study. Br Med J 1999, 319:1166-1167.
• [8]Aron Y, Polla BS, Bienvenu T, Dall'ava J, Dusser D, Hubert D: HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype. Am J Respir Crit Care Med 1999, 159:1464-1468.
• [9]Meng QH, Springall DR, Bishop AE, Morgan K, Evans TJ, Habib S, Gruenert DC, Gyi KM, Hodson ME, Yacoub MH, Polak JM: Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. J Pathol 1998, 184:323-331.
• [10]Kelley TJ, Drumm ML: Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest 1998, 102:1200-1207.
• [11]Grasemann H, Knauer N, Buscher R, Hubner K, Drazen JM, Ratjen F: Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene. Am J Respir Crit Care Med 2000, 162:2172-2176.
• [12]Hill AV: The immunogenetics of human infectious diseases. Annu Rev Immunol 1998, 16:593-617.
• [13]van Deventer SJ: Cytokine and cytokine receptor polymorphisms in infectious disease. Intensive Care Med 2000, 26:S98-S102.
• [14]Zhang P, Summer WR, Bagby GJ, Nelson S: Innate immunity and pulmonary host defense. Immunol Rev 2000, 173:39-51.
• [15]Hull J, Thomson AH: Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis. Thorax 1998, 53:1018-1021.
• [16]Ohno I, Lea RG, Flanders KC, Clark DA, Banwatt D, Dolovich J, Denburg J, Harley CB, Gauldie J, Jordana M: Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest 1992, 89:1662-1668.
• [17]Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S: Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993, 90:770-774.
• [18]Arkwright PD, Laurie S, Super M, Pravica V, Schwarz MJ, Webb AK, Hutchinson IV: TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax 2000, 55:459-462.
• [19]Parmley RR, Gendler SJ: Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus. J Clin Invest 1998, 102:1798-1806.
• [20]Smigielski EM, Sirotkin K, Ward M, Sherry ST: dbSNP: a database of single nucleotide polymorphisms. Nucl Acids Res 2000, 28:352-355.