Alpha1-antitrypsin deficiency alleles and the Taq-I G-->A allele in cystic fibrosis lung disease.
| Autoři: | Mahadeva R; Dept of Medicine, University of Cambridge, UK., Westerbeek RC, Perry DJ, Lovegrove JU, Whitehouse DB, Carroll NR, Ross-Russell RI, Webb AK, Bilton D, Lomas DA |
|---|---|
| Zdroj: | The European respiratory journal [Eur Respir J] 1998 Apr; Vol. 11 (4), pp. 873-9. |
| Způsob vydávání: | Journal Article; Research Support, Non-U.S. Gov't |
| Jazyk: | English |
| Informace o časopise: | Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Print Cited Medium: Print ISSN: 0903-1936 (Print) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE |
| Imprint Name(s): | Publication: Sheffield, United Kingdom : European Respiratory Society Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988- |
| Výrazy ze slovníku MeSH: | Cystic Fibrosis/*genetics , alpha 1-Antitrypsin Deficiency/*genetics, Adult ; Alleles ; C-Reactive Protein/genetics ; Cystic Fibrosis/physiopathology ; Female ; Humans ; Lung/physiopathology ; Male ; Phenotype ; alpha 1-Antichymotrypsin/genetics |
| Abstrakt: | Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G-->A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin. |
| Substance Nomenclature: | 0 (alpha 1-Antichymotrypsin) 9007-41-4 (C-Reactive Protein) |
| Entry Date(s): | Date Created: 19980612 Date Completed: 19980727 Latest Revision: 20190822 |
| Update Code: | 20240829 |
| DOI: | 10.1183/09031936.98.11040873 |
| PMID: | 9623690 |
| Autor: | Mahadeva R; Dept of Medicine, University of Cambridge, UK., Westerbeek RC, Perry DJ, Lovegrove JU, Whitehouse DB, Carroll NR, Ross-Russell RI, Webb AK, Bilton D, Lomas DA |
| Jazyk: | angličtina |
| Zdroj: | The European respiratory journal [Eur Respir J] 1998 Apr; Vol. 11 (4), pp. 873-9. |
| DOI: | 10.1183/09031936.98.11040873 |
| Abstrakt: | Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G-->A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|