Sai K, Itoda M, Saito Y, Kurose K, Katori N, Kaniwa N, Komamura K, Kotake T, Morishita H, Tomoike H, Kamakura S, Kitakaze M, Tamura T, Yamamoto N, Kunitoh H, Yamada Y, Ohe Y, Shimada Y, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Ozawa S, Sawada J
Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, 158-8501, USA.
Ann Hum Genet. 2006 Sep;70(Pt 5):605-22. doi: 10.1111/j.1469-1809.2006.00260.x.
As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.
由于最近在该基因的启动子区域报道了功能性ABCB1单倍型，我们对总共533名日本受试者的ABCB1远端启动子区域以及其他区域（增强子和近端启动子区域，以及所有28个外显子）进行了重测序。基于92个遗传变异的连锁不平衡（LD）分析揭示了4个LD块，其组成与先前描述的相同（块-1、1、2和3），只是块1扩展到包括远端启动子区域，并且在远端启动子区域的多态性-1,789G>A与内含子5中的IVS5 + 123A>G之间发现了新的连锁。我们重新分配了块1单倍型，并在其他3个块中添加了新的单倍型。根据块1编码或内含子区域内的标签变异，将报道的启动子单倍型进一步分类为几种类型。我们目前的数据再次证实了其他三个块的单倍型概况，增加了日本人群中块1和2中功能重要单倍型的更详细信息，并确定了不同种族之间单倍型概况的差异。我们对ABCB1单倍型块的更新分析将有助于使用亚洲受试者进行的药物遗传学和疾病关联研究。
