title: Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations.
abstract: Human beta defensins contribute to the first line of defense against infection of the lung. Polymorphisms in these genes are therefore potential modifiers of the severity of lung disease in cystic fibrosis. Polymorphisms were sought in the human beta-defensin genes DEFB1, DEFB4, DEFB103A, and DEFB104 in healthy individuals and cystic fibrosis (CF) patients living in various European countries. DEFB1, DEFB4, and DEFB104 were very polymorphic, but DEFB103A was not. Within Europe, differences between control populations were found for some of the frequent polymorphisms in DEFB1, with significant differences between South-Italian and Czech populations. Moreover, frequent polymorphisms located in DEFB4 and DEFB104 were not in Hardy Weinberg equilibrium in all populations studied, while those in DEFB1 were in Hardy Weinberg equilibrium. Sequencing of a monochromosomal chromosome 8 mouse-human hybrid cell line revealed signals for multiple alleles for some loci in DEFB4 and DEFB104, but not for DEFB1. This indicated that more than one DEFB4 and DEFB104 gene was present on this chromosome 8, in agreement with recent findings that DEFB4 and DEFB104 are part of a repeat region. Individual DEFB4 and DEFB104 PCR amplification products of various samples were cloned and sequenced. The results showed that one DNA sample could contain more than two haplotypes, indicating that the various repeats on one chromosome were not identical. Given the higher complexity found in the genomic organization of the DEFB4 and DEFB104 genes, association studies with CF lung disease severity were performed only for frequent polymorphisms located in DEFB1. No association with the age of first infection by Pseudomonas aeruginosa or with the FEV1 percentage at the age of 11-13 years could be found.
authors.affiliation: Department of Human Genetics, KULeuven, Herestraat 49, O&N6, 3000 Louvain, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Vankeerberghen
authors.forename: Olga
authors.initials: O
authors.lastname: Scudiero
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Noémi
authors.initials: N
authors.lastname: Van Hul
authors.forename: Hilde
authors.initials: H
authors.lastname: Nuytten
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castaldo
authors.forename: Daniela
authors.initials: D
authors.lastname: Zemkova
authors.forename: Vera
authors.initials: V
authors.lastname: Vavrova
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: Harry
authors.initials: H
authors.lastname: Cuppens
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003550:Cystic Fibrosis / Q000235:genetics*; D005060:Europe; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins