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Genetic effects of the MHC and KIR locus on autoimmune d

MHC 和 KIR 位点对自身免疫性疾病的遗传影响

基本信息

批准号：
7338439
负责人：
Mary N. Carrington
金额：
--
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7338439
关键词：
Genetic effects MHC KIR locus

项目摘要

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.

我们已经完成了我们来自台湾的鼻咽癌队列中的人类白细胞抗原/KIR的基因分型和分析，我们的结果现已发表。我们最近完成了这个队列的KIR3DL2亚型，数据正在分析中。我们还开始了中国鼻咽癌队列的人类白细胞抗原基因分型工作。对我们的黑色素瘤队列的初步分析表明，与拥有全长等位基因的受试者相比，携带截短的KIR2DS4等位基因(可能是非功能性的)的受试者免受黑色素瘤风险的保护。这一点在病例对照和家庭研究中都很明显。这些结果有些令人费解，所以为了进一步探索我们的发现，我们已经开始研究其他与该等位基因连锁不平衡的KIR基因。根据我们在家系中的研究，我们已经确定KIR2DL4的某些等位基因与截短的KIR2DS4等位基因存在强烈的连锁不平衡。少数研究表明，KIR2DL4的配体是人类白细胞抗原G，通常主要表达于滋养层细胞，但也可能表达于黑色素瘤细胞，提示KIR2DL4是一个很好的候选基因。我们现在已经完成了KIR2DL4的亚型，初步分析表明确实存在与特定等位基因的关联，该特定等位基因与截短的KIR2DS4等位基因存在强烈的连锁不平衡。一旦分型完成，将开始对结直肠癌队列的数据进行分析。