Polymorphisms and disease associations of receptor gene families for class I antigens

对人类KIR、NKG2、LILR家族和NKp30基因的多态性进行了研究。在KIR家族中，分析了17个不同的KIR基因的谱型和单倍型。对于NKG2A、NKG2C和NKp30基因的多态性，分别检测到11、4和5个不同的等位基因。此外，我们还发现了NKG2C基因缺失的频繁发生。我们通过核苷酸测序进一步阐明了缺失的断裂点，并建立了检测杂合子缺失的体系。LILR家族中的ILT2基因也被发现有许多等位基因，其中一些与类风湿关节炎(RA)显著相关。带状疱疹与带状疱疹后神经痛(PHN)的相关性研究表明，一种特定的人类白细胞抗原单倍型易患带状疱疹后神经痛。此外，我们还发现一例新的人类白细胞抗原I类缺乏症是由于Tapasin基因的部分缺失引起的。在这种情况下，I类分子的表达水平下降幅度小于TAP1基因缺失。

Polymorphisms of human genes of KIR, NKG2, LILR families and NKp30 have been investigated. On the KIR family, profiles and haplotypes of 17 different KIR genes were analyzed. Concerning the NKG2A, NKG2C and NKp30 gene polymorphisms, 11, 4 and 5 different alleles have been identified, respectively. Moreover, we found the frequent occurrence of NKG2C gene deletion. We further elucidated the breakpoints of the deletion by nucleotide sequencing, and then established a system for detecting heterozygotes with deletion. The ILT2 gene in the LILR family was also found to have many alleles, and some of them showed significant associations with rheumatoid arthritis (RA). Association studies on herpes zoster and post-herpetic neuralgia (PHN) have been performed, and a specific HLA haplotype was shown to predispose susceptibility to PHN. Furthermore, we found that a new case of HLA class I deficiency was caused by a partial deletion of the Tapasin gene. In this case, decrease of the expression levels of class I molecules was less than that in the TAP1 gene deletion.