Figure 2

Distribution of TLR4 haplotypes and associated cytokine phenotypes across the 3 continents of the Old World. It shows that Africa, Asia, and Europe each have their own distinct haplotype, based on the alleles found, shown in white. The phenotypic end point is shown on the top of the figure, where the expected cytokine production following TLR4 stimulations is presented. When the geographic distribution of Asp299Gly and Thr399lle polymorphisms is taken into account, it illustrates that research preformed in Europe has looked at the cosegregated Asp299Gly/Thr399lle haplotype, whose cytokine phenotype does not differ from the wild-type TLR4 cytokine response. This also explains the large number of studies, performed in Europe, that did not find any association between TLR4 polymorphisms and susceptibility to disease. In contrast, the Asp299Gly/WT haplotype, that is found almost exclusively in Africa, has a stronger pro-inflammatory cytokine response compared with wild-type TLR4.