Association study between the CX3CR1 gene and asthma.

Universite´ du Que´bec a` Chicoutimi, Saguenay, Que´bec, CanadaCX3CR1, a fractalkine receptor, mediates cell-adhesive and migratory functions in inflammation. Based on CX3CR1expression observed in bronchial tissues of asthmatic subjects, we hypothesized that genetic variation at this locus may affectsusceptibility to asthma. We carried out an association study and haplotypic analyses with selected polymorphisms of theCX3CR1 in a familial asthmatic sample from a founder population. Genetic analyses performed by FBAT showed five CX3CR1single nucleotide polymorphisms (rs938203, rs2669849, rs1050592, T280M and V249I) with significant associations betweentheir common alleles and asthma (Po0.004) in a dominant model. A haplotype formed with common alleles of rs1050592,T280M and V249I is also overtransmitted in asthmatic subjects (P¼0.005) under a dominant model. The associations of V249Iand rs2669849 have been validated in an independent case–control sample. For V249I, odds ratios (OR) are 2.16 (commonhomozygous) and 2.11 (heterozygous) in dominant model (P¼0.031). For rs2669849, OR are 2.75 (common homozygous)and 1.86 (heterozygous) in additive model (P¼0.007) and dominant model (P¼0.059). These results suggest an asthmaprotective effect of the minor alleles in healthy control carriers. Further functional studies of CX3CR1 are needed to documentits role in the pathophysiology of asthma.Genes and Immunity (2006) 0, 000–000. doi:10.1038/sj.gene.6364340Keywords: association study; asthma; CX3CR1; polymorphisms; haplotypic analyses