doi: 10.1111/j.1469-1809.2006.00260.x Genetic Variations and Haplotype Structures of the ABCB1 Gene in a Japanese Population: An Expanded Haplotype Block Covering the Distal Promoter Region, and Associated Ethnic Differences K. Sai 1,2,* , M. Itoda 1 , Y. Saito 1,3 , K. Kurose 1,4 , N. Katori 1,5 , N. Kaniwa 1,4 , K. Komamura 7,8 , T. Kotake 9 , H. Morishita 9 , H. Tomoike 7 , S. Kamakura 7 , M. Kitakaze 7 , T. Tamura 10 , N. Yamamoto 10 , H. Kunitoh 10 , Y. Yamada 11 , Y. Ohe 10 , Y. Shimada 11 , K. Shirao 11 , H. Minami 12 , A. Ohtsu 13 , T. Yoshida 14 , N. Saijo 15 , N. Kamatani 16 , S. Ozawa 1,6 and J. Sawada 1,3 1 Project Team for Pharmacogenetics, 2 Division of Xenobiotic Metabolism and Disposition, 3 Biochemistry and Immunochemistry, 4 Division of Medicinal Safety Science, 5 Division of Drugs, 6 Division of Pharmacology, National Institute of Health Sciences, Tokyo, 158-8501 7 Division of Cardiology, 8 Department of Cardiovascular Dynamics Research Institute, 9 Department of Pharmacy, National Cardio- vascular Center, Suita, 565-8565 10 Thoracic Oncology Division, 11 Gastrointestinal Oncology Division, National Cancer Center Hospital, 14 Genetics Division, National Cancer Center Research Institute, Tokyo, 104-0045 12 Division of Oncology/Hematology, 13 Division of GI Oncology/Digestive Endoscopy, 15 National Cancer Center Hospital East, Kashiwa, 277-8577 and 16 Division of Genomic Medicine, Department of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, 162-0054, Japan Summary 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 − 1789G>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. Keywords: ABCB1, P-gp, haplotype ∗ Correspondence to: Dr. Kimie Sai, Division of Xenobi- otic Metabolism and Disposition, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. Tel. +81-3-3700-9478; Fax: +81-3-3707-6950, E-mail: sai@nihs.go.jp Introduction The ABCB1 gene, encoding p-glycoprotein (P-gp)/multidrug resistance protein 1 (MDR1), is located on chromosome 7q21-q31 and consists of 28 exons. P-gp (1280 amino acids), a member of the C  2006 The Authors Annals of Human Genetics (2006) 70,605–622 605 Journal compilation C  2006 University College London