A polymorphism in ADRB2 gene is associated with severity of pulmonary phenotype in Cystic Fibrosis patients.

• Authors: Stefania Lenarduzzi , Ludovica Segat , Sergio Crovella , Luisa Zupin , Annalisa Fabris , Alessandro Amaddeo , Chiara Trevisiol , Furio Poli , Marcello Morgutti
• Languages of publication: EN

Abstracts

EN

Background: Cystic Fibrosis (CF) is a common genetic disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein. It is known that modifier genes and environmental factors play a key role in determining the severity of the disease. Methods: We analyzed Single Nucleotide Polymorphisms (SNPs) in three genes, namely TNFA, TGFB1 and ADRB2, as potential modifiers of CF lung phenotype: c.−851C>T, c.−308G>A, c.−238G>A and c.+691G ins/del SNPs in TNFA, p.Leu10Pro (c.869C>T) and p.Arg25Pro (c.915G>C) SNPs in TGFB1 and p.Arg16Gly (c.46G>A), p.Gln27Glu (c.79C>G) and p.Thr164Ile (c.491C>T) in ADRB2. Results: For the c.46G>A SNP of ADRB2 the A allele (Arg16), as well as the AA genotype, were significantly more frequent in CF patients than healthy controls. When stratifying CF patients according to FEV1 (Forced Expiratory Volume in 1 second) phenotype we observed a statistically significant difference (p=0.02) in the allelic and genotype frequencies. The A allele and A/A genotype were more frequent in mild CF patients when compared to severe CF subjects and thus probably associate with a protective effect toward the development of severe pulmonary manifestation in CF patients. Conclusions: Our results are indicative of the involvement of the ADRB2 gene as modifier gene in Cystic Fibrosis pulmonary phenotype.

Keywords

EN

Cystic Fibrosis; Modifier genes; Tumor necrosis factor-α (TNFA); Transforming growth factor-β1 (TGFB1); β2 adrenergic receptor (ADRB2); Pulmonary manifestation; Polymorphism

• Publisher: De Gruyter Open
• Journal: Genetics of Multifactorial Disorders
• Year: 2014
• Volume: 1
• Pages: 6-11

Dates

online

24 - 02 - 2014

accepted

3 - 11 - 2013

received

5 - 4 - 2013

Contributors

author

Stefania Lenarduzzi

• IRCCS Burlo Garofolo, Via dell’Istria 65⁄1. 34137 Trieste, Italy

author

Ludovica Segat

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

author

Sergio Crovella

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, University of Trieste, Italy

author

Luisa Zupin

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

author

Annalisa Fabris

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

author

Alessandro Amaddeo

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

author

Chiara Trevisiol

• Pediatric Unit, San Polo Hospital, Via Galvani 1, 34074 Monfalcone (GO), Italy

author

Furio Poli

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

author

Marcello Morgutti

• Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” – via dell’Istria 65/1, 34100 Trieste, Italy

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Identifiers

DOI

10.2478/gmd-2014-0002