Akiyama Fumihiro, Tanaka Toshihiro, Yamada Ryo, Ohnishi Yozo, Tsunoda Tatsuhiko, Maeda Shiro, Takei Takashi, Obara Wataru, Ito Kyoko, Honda Kazuho, Uchida Keiko, Tsuchiya Ken, Nitta Kosaku, Yumura Wako, Nihei Hiroshi, Ujiie Takashi, Nagane Yutaka, Miyano Satoru, Suzuki Yasushi, Fujioka Tomoaki, Narita Ichiei, Gejyo Fumitake, Nakamura Yusuke
Human Genome Center, The Institute of Medical Science, University of Tokyo, Japan.
J Hum Genet. 2002;47(10):532-8. doi: 10.1007/s100380200080.
Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that SNPs located in the HLA- DRA gene were significantly associated with an increased risk of IgAN ( P = 0.000001, odds ratio = 1.91 [95% confidence interval 1.46-2.49]); SNPs in other LD blocks were not. Our data imply that some haplotype of the HLA- DRA locus has an important role in the development of IgAN in Japanese patients.
免疫球蛋白A肾病（IgAN）是一种病因和发病机制不明的慢性肾小球肾炎。免疫遗传学研究尚未确凿表明人类白细胞抗原（HLA）与之有关。作为研究HLA II类基因与IgAN之间可能关系的第一步，我们在一个日本测试人群中分析了6号染色体p21.3区域的连锁不平衡（LD）程度，发现在II类基因座内存在扩展的LD块。我们针对这些LD块中的每一个设计了单核苷酸多态性（SNP）的病例对照关联研究，并确定位于HLA-DRA基因中的SNP与IgAN风险增加显著相关（P = 0.000001，优势比 = 1.91 [95%置信区间1.46 - 2.49]）；其他LD块中的SNP则不然。我们的数据表明，HLA-DRA基因座的某些单倍型在日本患者IgAN的发生中起重要作用。
