Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus

Interleukin-8 (IL8) is believed to play a role in the pathogenesis of bronc hiolitis, a common viral disease of infancy, and a recent U.K. family study identified an association between this disease and the IL8-251A allele. In the present study we report data, from a different set of families, which replicate this finding; combined analysis of 194 nuclear families through u se of the transmission/disequilibrium test gives. To explore the underlying genetic cause, we identified nine single-nucleotide polymorphisms (SNPs) i n a 7.6-kb segment spanning the IL8 gene and its promoter region and used s ix of these SNPs to define the haplotypic structure of the IL8 locus. The I L8-251A allele resides on two haplotypes, only one of which is associated w ith disease, suggesting that this may not be the functional allele. Europea ns show an unusual haplotype genealogy that is dominated by two common hapl otypes differing at multiple sites, whereas Africans have much greater hapl otypic diversity. These marked haplotype-frequency differences give an F-ST of .25, and, in the European sample, both Tajima's D statistic (D = 2.58, P = .007) and the Hudson/Kreitman/Aguade test (chi (2) = 4.9, P = .03) reje ct neutral equilibrium, suggesting that selective pressure may have acted o n this locus.