ABCMdb

PMID: 11175304

de Cid R, Chomel JC, Lazaro C, Sunyer J, Baudis M, Casals T, Le Moual N, Kitzis A, Feingold J, Anto J, Estivill X, Kauffmann F
CFTR and asthma in the French EGEA study.
Eur J Hum Genet. 2001 Jan;9(1):67-9., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Results regarding ∆F508 come from a Danish study conducted in about 9000 subjects from the general population.1 However, the hypothesis that ∆F508 heterozygosity in the CFTR gene could protect against asthma, was proposed earlier after a study conducted in obligate heterozygotes.3 Recently, a case control study based on 144 asthmatics recruited in emergency rooms in Barcelona and a first control group of 41 spouses of CF carriers showed an excess of heterozygotes for aminoacid variants in the asthmatics, R75Q, G576A, R668C and L997F being the most frequent. Login to comment 8 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Due to the work load, only the four most common variants previously observed in asthmatics (R75Q, G576A, R668C and L997F), which accounted for 50% of mutations in asthmatics in the Barcelona study, were typed in the EGEA study as previously in the second control group in Barcelona, using the same techniques.2 The most common mutation in cystic fibrosis, ∆F508 was analysed by acrylamide gel electrophoresis, and the missense variant M470V8 was analysed by DGGE. Login to comment 10 ABCC7 p.Arg75Gln ABCC7 p.Gly576Ala Three missense variants R75Q,10 G576A,11 L997F11 were analyzed by restriction analysis. Login to comment 11 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Variant R668C11 was analyzed by SSC A. Prevalences in the whole sample of 480 subjects were 2.9%, 3.8%, 4.0%, 4.2% and 0.6% for heterozygosity for ∆F508, R75Q, G576A, R668C and L997F, respectively. Login to comment 18 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Any variant (R75Q, R668C, G576A, L997F), carriers of M allele (M470V), or 5T/-, shows odds ratios lower than 1, which were not statistically significant, except for 5T/-. Login to comment 35 ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Although differences in population could explain the differences between asthmatics in Barcelona and in France, the most likely hypothesis is that the four variants which were unusually frequent in the asthmatics in the first study do not relate to asthma, since a similar distribution to that of Table 1 Comparison of cases and controls from the EGEA study Controls: no asthma P value Asthma cases Both parents: no asthma OR [95% CI] Number 247 174 Demographic and clinical characteristics Geographical origin within France Paris, % 24.9 25.8 0.98 North West, % 11.0 9.8 South West, % 5.3 4.6 North East, % 6.9 8.1 South East, % 51.8 51.7 Age, m±SD 30.2±17.9 34.7±16.1 0.01 [range] [7.0-68.8] [7.4-64.7] Sex, % males 57.1 49.4 0.12 Atopy (weal ≥ 3mm, any of 11 allergens), % 76.8 34.8 0.001 6.4 [4.2-9.7] IgE, IU/ml, GM 246 36 0.001 Hay fever or childhood eczema, % 61.4 30.5 0.001 3.6 [2.4-5.5] FEV1 % predicted, m±SD 0.88±0.19 1.04±0.15 0.001 FVC % predicted, m±SD 0.99±0.16 1.04±0.15 0.001 Methacholine challenge, numbera 113 127 PD20 ≤ 4mg, % 92.9 22.8 0.001 44.4 [22.4-87.8] CFTR data ∆F508, % 3.2 2.9 0.83 1.13 [0.36-3.52] R75Q, % 2.4 5.2 0.14 0.46 [0.16-1.28] G576A, % 3.6 4.0 0.84 0.90 [0.33-2.47] R668C, % 3.6 4.6 0.62 0.79 [0.30-2.07] L997F, % 0.4 0.6 1.0b R75Q or G576A or R668C or L997F, % 6.9 9.8 0.28 0.68 [0.34-1.37] M470V MM, % 18.2 17.2 MV, % 46.2 50.6 0.66 VV, % 35.6 32.2 IVS8-(T) n, 5T/-, % 6.9 12.6 0.05 0.51 [0.27-0.99] a FEV1 > 80% predicted and no contraindications. Login to comment