Genetic effects of the MHC and KIR locus on autoimmune d

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We have completed genotyping and analysis of HLA/KIR in our NPC cohort from Taiwan and our results have now been published. We recently completed KIR3DL2 subtyping on this cohort and the data are being analyzed. We have also begun HLA genotyping on the Chinese NPC cohort. Preliminary analysis of our melanoma cohort indicate that subjects carrying a truncated KIR2DS4 allele (which might be nonfunctional), are protected against the risk of melanoma when compared with subjects who have the full length allele. This was evident in both the case-control and family studies. These results are somewhat puzzling, so to further explore our findings we have begun to study other KIR genes that are in linkage disequilibrium with this allele. Based on our studies in families, we have determined that certain alleles of KIR2DL4 are in strong linkage disequilibrium with the truncated KIR2DS4 allele. A few studies have shown that the ligand for KIR2DL4 is HLA-G, which is normally expressed primarily on trophoblast cells, but may also be expressed by melanoma cells, suggesting that KIR2DL4 is a good candidate gene in this disease. We have now completed subtyping of KIR2DL4 and preliminary analysis suggests that indeed there is an association with a specific allele that is in strong linkage disequilibrium with the truncated KIR2DS4 allele. Analysis of the data from the colorectal cancer cohort will begin once the typing is complete.