Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy

<b>Background and Objectives</b> : Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 &#60; 300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. <b> Methods</b> : We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. <b> Results</b> : From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. <b> Conclusion</b> : The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5&#8710;32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene