Highly preferential association of NonF508del CF mutations with the M470 allele

• Published in: Journal of cystic fibrosis Vol. 6; no. 1; pp. 15 - 22
• Main Authors: Ciminelli, B.M, Bonizzato, A, Bombieri, C, Pompei, F, Gabaldo, M, Ciccacci, C, Begnini, A, Holubova, A, Zorzi, P, Piskackova, T, Macek, M, Castellani, C, Modiano, G, Pignatti, P.F
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2007
• Subjects: CF risk; CFTR; Cystic Fibrosis - ethnology; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Czech Republic - ethnology; DNA Mutational Analysis; European Continental Ancestry Group - genetics; Female; Gene Frequency - genetics; Genetic Testing - methods; Haplotype; Heterozygote; Humans; Italy - ethnology; M470V polymorphism; Male; Mutation; Pilot Projects; Polymorphism, Single Nucleotide - genetics; Pulmonary/Respiratory; Risk; Italy; Czech Republic; CF risk; M470V polymorphism; Haplotype; CFTR
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2006.04.003

Abstract Background On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. Methods We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. Results Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9× greater than VV subjects when F508del is excluded and 15.4× when F508del is included. In the Czech population a similar, although less pronounced, association is observed. Conclusions Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.