Prostaglandin-endoperoxide synthase genes COX1 and COX2 - novel modifiers of disease severity in cystic fibrosis patients

• Autorzy: Czerska K. , Sobczynska-Tomaszewska A. , Sands D. , Nowakowska A. , Bak D. , Wertheim K. , Poznanski J. , Zielenski J. , Norek A. , Bal J.
• Języki publikacji: EN

Abstrakty

EN

Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among Caucasians caused by a mutation in the CFTR gene. However, the clinical outcome of CF pulmonary disease varies remarkably even in patients with the same CFTR genotype. This has led to a search for genetic modifiers located outside the CFTR gene. The aim of this study was to evaluate the effect of functional variants in prostaglandin-endoperoxide synthase genes (COX1 and COX2) on the severity of lung disease in CF patients. To the best of our knowledge, it is the first time when analysis of COX1 and COX2 as potential CF modifiers is provided. The study included 94 CF patients homozygous for F508del mutation of CFTR. To compare their' clinical condition, several parameters were recorded, e.g. a unique clinical score: disease severity status (DSS). To analyse the effect of non-CF7X genetic polymorphisms on the clinical course of CF patients, the whole coding region of COX 1 and selected COX2 polymorphisms were analysed. Statistical analysis of genotype-phenotvpe associations revealed a relationship between the heterozygosity status of identified polymorphisms and better lung function. These results mainly concern COX2 polymorphisms: -765G>C and 8473T>C. The COX1 and COX2 polymorphisms reducing COX protein levels had a positive effect on all analysed clinical parameters. This suggests an important role of these genes as protective modifiers of pulmonary disease in CF patients, due to inhibition of arachidonic acid conversion into prostaglandins, which probably reduces the inflammatory process.

Słowa kluczowe

EN

human disease; cystic fibrosis; patient; lung disease; gene; prostaglandin; disease expression; pulmonary inflammation; Pseudomonas aeruginosa; Staphylococcus aureus; Burkholderia cepacia; phenotypic variability

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 2010
• Tom: 51
• Numer: 3
• Opis fizyczny: p.323-330,fig.,ref.

Twórcy

autor

Czerska K.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland
• Postgraduate School of Molecular Medicine, Warsaw, Poland

autor

Sobczynska-Tomaszewska A.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland

autor

Sands D.

autor

Nowakowska A.

• Institute of Mother and Child, Department of Paediatrics, Warsaw, Poland

autor

Bak D.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland
• Postgraduate School of Molecular Medicine, Warsaw, Poland

autor

Wertheim K.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland

autor

Poznanski J.

• Institute of Biochemistry and Biophysics, Department of Biophysics, Warsaw, Poland

autor

Zielenski J.

• Hospital for Sick Children, Program in Genetics and Genome Biology, Toronto, Ontario, Canada

autor

Norek A.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland

autor

Bal J.

• Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland

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