ABCMdb

PMID: 18652532

Stankovic M, Nikolic A, Divac A, Tomovic A, Petrovic-Stanojevic N, Andjelic M, Dopudja-Pantic V, Surlan M, Vujicic I, Ponomarev D, Mitic-Milikic M, Kusic J, Radojkovic D
The CFTR M470V gene variant as a potential modifier of COPD severity: study of Serbian population.
Genet Test. 2008 Sep;12(3):357-62., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Arg75Gln As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Login to comment 37 ABCC7 p.Arg75Gln The R75Q polymorphism, not as frequent as M470V and 5T variants, was found to be significantly more frequent in patients with atypical CF (Hughes et al., 2001). Login to comment 39 ABCC7 p.Arg75Gln As it is known that certain CFTR variants may have a consequence on function of CFTR protein, the aim of this study was to examine the role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation concerning severity and onset of the disease. Login to comment 52 ABCC7 p.Arg75Gln The R75Q polymorphism (356G=A in exon 3) was detected by denaturing gradient gel electrophoresis method, and its presence was confirmed by automated sequencing (ALFexpress 2.0 DNA sequencer; Pharmacia Biotech, Vienna, Austria) (Fanen et al., 1992). Login to comment 66 ABCC7 p.Arg75Gln All genotype distributions were in Hardy-Weinberg equilibrium, with the exception of R75Q polymorphism in COPD group. Login to comment 68 ABCC7 p.Arg75Gln We have observed no association of F508del, M470V, 5T, and R75Q genetic variants with COPD status, while corresponding statistical powers were 0.31, 0.05, 0.10, and 0.18, respectively. Login to comment 79 ABCC7 p.Arg75Gln Association of F508del, 5T, and R75Q variants of CFTR gene with COPD severity was not observed. Login to comment 80 ABCC7 p.Arg75Gln Discussion This study was undertaken to assess the role of F508del mutation and three common CFTR variants, M470V, IVS8-5T, and R75Q, in the etiology of COPD. Login to comment 94 ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln Allelic Frequencies and Genotype Distribution of CFTR Gene Variants in COPD Group and Controls Genotype=allele distribution COPD Controls OR (95%CI)a p-valuea F508del F508del=wtb 5 (5.8) 1 (1.0) 8.00 (0.82-77.98) 0.073 F508 allelec 0.029 0.005 0.10 M470V MM 18 (21.0) 18 (17.6) MV 37 (43.0) 48 (47.1) VV 31 (36.0) 36 (35.3) 0.98 (0.50-1.95) 0.96 V allelec 0.576 0.588 0.83 Tn locus 9T=9T 2 (2.3) 1 (1.0) 7T=9T 16 (18.6) 18 (17.6) 7T=7T 56 (65.1) 73 (71.6) 5T=9T 3 (3.5) 2 (2.0) 1.39 (0.51-3.79)d 0.52 5T=7T 9 (10.5) 8 (7.8) 5T allelec 0.070 0.050 0.51 R75Q R75Q=wtb 4 (4.6) 2 (2.0) 3.59 (0.55-23.28)e 0.18 R75Q=R75Q 1 (1.2) 0 (0.0) R75Q allelec 0.035 0.010 0.15 a Adjusted for age, sex, and cumulative cigarette consumption. b wt: wild type. c p-values were calculated using Fisher`s exact test. Login to comment 96 ABCC7 p.Arg75Gln e Presence of at least one R75Q allele versus wt=wt genotype was tested. Login to comment 103 ABCC7 p.Arg75Gln The frequency of R75Q variant carriers was not significantly increased in comparison to control group (5.8% Table 4. Login to comment 104 ABCC7 p.Arg75Gln Analysis of CFTR Allele Variants and Their Association with COPD Severity FEV1 Genotype <50% pred $50% pred OR (95%CI)a p-valuea COPD patients (n) 56 30 F508del wt=wtb 53 (94.6) 28 (93.3) F508del=wtb 3 (5.4) 2 (6.7) 0.70 (0.10-4.95) 0.72 M470V MM 16 (28.6) 2 (6.7) 4.28 (0.88-20.75)c 0.07c MV 25 (44.6) 12 (40.0) VV 15 (26.8) 16 (53.3) 0.29 (0.11-0.80)d 0.016d Tn locus 9T=9T, 7T=9T, and 7T=7T 49 (87.5) 25 (83.3) 5T=9T and 5T=7T 7 (12.5) 5 (16.7) 0.80 (0.22-2.92) 0.73 R75Q wt=wtb 52 (92.9) 29 (96.7) R75Q=wtb and R75Q=R75Q 4 (7.1) 1 (3.3) 2.35 (0.22-25.49) 0.48 a Adjusted for age, sex, and cumulative cigarette consumption. b wt: wild type. c MM versus MV and VV was tested. d VV versus MV and MM was tested. Login to comment 106 ABCC7 p.Arg75Gln Analysis of CFTR Allele Variants and Their Association with Disease Onset Disease onset Genotype <40 years $40 years OR (95%CI)a p-valuea COPD patients (n) 23 63 F508del wt=wtb 21 (91.3) 60 (95.2) F508del=wtb 2 (8.7) 3 (4.8) 3.90 (0.26-57.30) 0.32 M470V MM 6 (26.1) 12 (19.0) 4.45 (0.48-41.28)c 0.19c MV 12 (52.2) 25 (39.7) VV 5 (21.7) 26 (41.3) 0.25 (0.03-2.16)d 0.21d Tn locus 9T=9T, 7T=9T, and 7T=7T 20 (87.0) 54 (85.7) 5T=9T and 5T=7T 3 (13.0) 9 (14.3) 2.19 (0.16-30.28) 0.56 R75Q wt=wtb 22 (95.7) 59 (93.7) R75Q=wtb and R75Q=R75Q 1 (4.3) 4 (6.3) 0.11 (0.00-55.5) 0.49 a Adjusted for age, sex, and cumulative cigarette consumption. b wt: wild type. c MM versus MV and VV was tested. d VV versus MV and MM was tested. Login to comment 108 ABCC7 p.Arg75Gln However, it should be mentioned that the R75Q variant was not in Hardy-Weinberg equilibrium in patient group (w2 ¼ 8.2, df ¼ 1, p < 0.05). Login to comment 109 ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln Considering the frequency of R75Q allele (3.5%), the R75Q homozygote was not expected. Login to comment 110 ABCC7 p.Arg75Gln This might be due to sampling variation or small sample size, but also might implicate importance of R75Q variant in pathology of COPD. Login to comment 111 ABCC7 p.Arg75Gln In our previous study, the frequency of R75Q polymorphism was significantly higher in COPD group than in healthy population (8.06% vs. 0.97%) (Divac et al., 2004). Login to comment 112 ABCC7 p.Arg75Gln In the present study conducted on a larger cohort of COPD patients, no statistical significance was achieved for R75Q variant in comparison to control group. Login to comment 113 ABCC7 p.Arg75Gln Despite that, nearly three times higher frequencies of R75Q carriers, as well as its genotype distribution disequilibrium, were observed in the patient group. Login to comment 115 ABCC7 p.Arg75Gln Although we were not able to obtain family members for the haplotype analysis of tested CFTR variants, we observed the complete association of R75Q variant with V470 allele. Login to comment 135 ABCC7 p.Arg75Gln Although the F508del, 5T, and R75Q alleles were more frequent in patients` group, the distribution of tested CFTR variants showed no statistical significance between COPD patients and controls. Login to comment