OBJECTIVE: The aim of this study was to characterize the population frequency of SLCO1B1 polymorphic variants in three distinct healthy Asian populations, namely Chinese (n = 100), Malay (n = 100) and Indian (n = 100), and to explore the association between haplotype-tagged single nucleotide polymorphisms (htSNPs) on hepatic SLCO1B1 mRNA expression. METHODS: The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients. RESULTS: Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A (P = 0.030)] as well as three coding region SNPs [c.388G>A (P < 0.001); c.571T>C (P < 0.001); c.597C>T (P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP. CONCLUSION: Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations.
OBJECTIVE: The aim of this study was to characterize the population frequency of SLCO1B1 polymorphic variants in three distinct healthy Asian populations, namely Chinese (n = 100), Malay (n = 100) and Indian (n = 100), and to explore the association between haplotype-tagged single nucleotide polymorphisms (htSNPs) on hepatic SLCO1B1 mRNA expression. METHODS: The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients. RESULTS: Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A (P = 0.030)] as well as three coding region SNPs [c.388G>A (P < 0.001); c.571T>C (P < 0.001); c.597C>T (P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP. CONCLUSION: Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations.
Authors: T Abe; M Kakyo; T Tokui; R Nakagomi; T Nishio; D Nakai; H Nomura; M Unno; M Suzuki; T Naitoh; S Matsuno; H Yawo Journal: J Biol Chem Date: 1999-06-11 Impact factor: 5.157
Authors: G A Kullak-Ublick; M G Ismair; B Stieger; L Landmann; R Huber; F Pizzagalli; K Fattinger; P J Meier; B Hagenbuch Journal: Gastroenterology Date: 2001-02 Impact factor: 22.682
Authors: C D Drenberg; S W Paugh; S B Pounds; L Shi; S J Orwick; L Li; S Hu; A A Gibson; R C Ribeiro; J E Rubnitz; W E Evans; A Sparreboom; S D Baker Journal: Clin Pharmacol Ther Date: 2016-02-20 Impact factor: 6.875
Authors: A Daka Grapci; A J Dimovski; A Kapedanovska; M Vavlukis; A Eftimov; N Matevska Geshkovska; N Labachevski; K Jakjovski; D Gorani; S Kedev; K Mladenovska Journal: Balkan J Med Genet Date: 2015-12-30 Impact factor: 0.519