ABCMdb

PMID: 15463907

Divac A, Nikolic A, Mitic-Milikic M, Nagorni-Obradovic L, Petrovic-Stanojevic N, Dopudja-Pantic V, Nadaskic R, Savic A, Radojkovic D
High frequency of the R75Q CFTR variation in patients with chronic obstructive pulmonary disease.
J Cyst Fibros. 2004 Aug;3(3):189-91., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Arg75Gln High frequency of the R75Q CFTR variation in patients with chronic obstructive pulmonary disease Aleksandra Divaca , Aleksandra Nikolica , Marija Mitic-Milikicb , Ljudmila Nagorni-Obradovicb , Natasa Petrovic-Stanojevicc , Vesna Dopudja-Panticc , Ruzica Nadaskicd , Ana Savica , Dragica Radojkovica,* a Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444A, 11000 Belgrade, Serbia and Montenegro b Institute for Tuberculosis and Lung Disease, University Clinical Center of Serbia, Belgrade, Serbia and Montenegro c Department of Pulmonology, University Clinical Center Zvezdara, Belgrade, Serbia and Montenegro d Department of Pulmonology, University Clinical Center Zemun, Belgrade, Serbia and Montenegro Received 24 March 2004; accepted 17 May 2004 Available online 25 July 2004 Abstract We performed the complete screening of the CFTR gene in a group of 31 patients with COPD in order to investigate the impact of mutations and polymorphisms in the CFTR gene. Login to comment 2 ABCC7 p.Arg75Gln The R75Q was significantly overrepresented in COPD patients (8.06%; P= 0.002). Login to comment 3 ABCC7 p.Arg75Gln In all patients carrying the R75Q chronic bronchitis was a dominant symptom of COPD, and all were homozygous for the V470 allele. Login to comment 4 ABCC7 p.Arg75Gln These findings suggest that R75Q mutation could be characteristic CFTR variant for COPD patients. Login to comment 6 ABCC7 p.Arg75Gln Keywords: Chronic obstructive pulmonary disease (COPD); CFTR; R75Q 1. Login to comment 39 ABCC7 p.Arg74Trp ABCC7 p.Arg75Gln ABCC7 p.Gly126Asp ABCC7 p.Phe1052Val ABCC7 p.Leu997Phe Six different mutations (R75Q, F508del, G126D, L997F, F1052V, R74W) were identified on 11 (17.74%) of the 62 chromosomes, giving a significantly higher frequency than in our general population ( P < 0.0001, 95%CI: 2.60-36.21). Login to comment 44 ABCC7 p.Arg75Gln Only the gene variant R75Q stood out as the most frequent one (5/62 chromosomes, 8.06%). Login to comment 45 ABCC7 p.Arg75Gln R75Q is a consequence of a nucleotide change from guanine to adenine at the position 356 in CFTR gene, which leads to an amino acid change from arginine to glutamine. Login to comment 47 ABCC7 p.Arg75Gln Although Zielinski initially reported R75Q as a DNA variant [17], it is possible that it represents a mild CFTR mutation. Login to comment 49 ABCC7 p.Arg75Gln The frequency of R75Q in COPD patients was significantly higher than in Serbian general population ( P= 0.002, 95%CI: 2.15-55.63). Login to comment 50 ABCC7 p.Arg75Gln In all patients carrying the R75Q, CB was a dominant symptom of COPD, they were all non-smokers, and their FEV1 values were below 50% of predicted. Login to comment 52 ABCC7 p.Arg75Gln Several groups have reported R75Q in patients with DB (1/23 patients in Italian patients with DB [6], 4/32 French DB patients [8]), CBAVD (4/37 Slovenian CBAVD patients [9]), CP (2/20 German CP patients [10]), and asthma (1/20 Greek asthma patients [7]). Login to comment 54 ABCC7 p.Arg75Gln R75Q was the most frequent, but not with significantly higher frequency, in the group of patients with DB (2/38 chromosomes). Login to comment 56 ABCC7 p.Arg75Gln As far as we know these are the first findings observing the increased frequency of R75Q mutation in patients with COPD having CB as a dominant symptom. Login to comment 58 ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln Also, it would be interesting to investigate functional consequences of R75Q alone, as well as a possible synergistic effect of R75Q and V470 allele. Login to comment 59 ABCC7 p.Arg74Trp ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Gly126Asp ABCC7 p.Phe1052Val ABCC7 p.Leu997Phe Table 1 CFTR genotypes in COPD patients No. of cases CFTR gene mutation IVS8 Tn M470V genotype 1 R75Q/R75Q 7/7 V470/V470 1 L997F/R75Q 7/9 V470/V470 2 R75Q/- 7/7 V470/V470 1 F508del/- 7/9 M470/V470 1 F508del/- 5/9 M470/M470 1 G126D/- 7/9 M470/M470 1 F1052V/- 7/7 M470/V470 1 R74W/- 7/7 M470/M470 2 -/- 5/7 V470/V470 3 -/- 5/7 M470/V470 1 -/- 5/7 M470/M470 1 -/- 5/9 M470/V470 3 -/- 7/9 M470/V470 6 -/- 7/7 V470/V470 4 -/- 7/7 M470/V470 -/- 7/7 M470/M470 A. Divac et al. / Journal of Cystic Fibrosis 3 (2004) 189-191190 Acknowledgements This work was supported by grant 1417 from Ministry for Science, Technologies and Development of Serbia. Login to comment