Genetic effects of the MHC and KIR locus on autoimmune d

我们已经完成了来自台湾的NPC队列的HLA/KIR基因分型和分析，我们的结果现已发表。我们最近完成了该队列的KIR 3DL 2亚型分型，数据正在分析中。我们还开始了中国NPC队列的HLA基因分型。我们的黑色素瘤队列的初步分析表明，与具有全长等位基因的受试者相比，携带截短的KIR 2DS 4等位基因（可能是无功能的）的受试者免受黑色素瘤风险的影响。这在病例对照研究和家庭研究中都很明显。这些结果有些令人困惑，因此为了进一步探索我们的发现，我们已经开始研究与该等位基因连锁不平衡的其他KIR基因。基于我们在家系中的研究，我们已经确定KIR 2DL 4的某些等位基因与截短的KIR 2DS 4等位基因处于强连锁不平衡。一些研究表明，KIR 2DL 4的配体是HLA-G，其通常主要在滋养层细胞上表达，但也可以由黑素瘤细胞表达，这表明KIR 2DL 4是该疾病的良好候选基因。我们现在已经完成了KIR 2DL 4的分型，初步分析表明，确实存在与特定等位基因的关联，该等位基因与截短的KIR 2DS 4等位基因处于强连锁不平衡。一旦分型完成，将开始对来自结直肠癌队列的数据进行分析。

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.