Frequency distribution of phenol sulfotransferase 1A1 activity in platelet cells from healthy Japanese subjects

Aims: To determine the distribution of sulfotransferase 1A1 (SULT1A1) activities, we used trans-4-hydroxytamoxifen (OHT) as a substrate to test samples from a Japanese population to examine whether the SULT1A1*2 allele can account for the wide distribution of OHT sulfating activity. We also studied genetic mutations other than the SULT1A1*2 allele to determine the cause of differences in SULT1A1 protein expression and activity. Methods: The subjects were 103 healthy Japanese adults. Identification of SULT1A1 genotypes was performed using a polymerase chain reaction-restriction fragment length polymorphism method. SULT1A1 activity in platelet cytosol was assayed using OHT as a substrate. SULT1A1 protein was detected using Western blotting analysis. Mutations other than SULT1A1*2 in the SULT1A1 gene were detected using sequencing analysis. Results: SULT1A1*2 allele frequency was found to be 16.5%, while SULT1A1 activity ranged from 63 to 1860 pmol sulfated/h/mg platelet protein (260 +/- 241 pmol sulfated/h/mg platelet protein, median +/- S.D.) using OHT as a substrate. The median values in subjects with SULT*1/*2 (221 +/- 113 pmol sulfated/h/mg platelet protein, range 63-442, n = 26) and SULT*2/*2 (124 +/- 166 pmol sulfated/h/mg platelet protein, range 74-231, n = 4) were significantly lower than that in subjects with SULT*1/*1 (303 +/- 267 pmol sulfated/h/mg platelet protein, range 97-1859, n = 73). A novel G148C mutation was found in one subject, who showed the lowest OHT sulfating activity; for a frequency of 0.49%. Conclusion: There was wide variety of OHT sulfating activities found among the present healthy Japanese subjects. The SULT1A1*2 allele was found to be a common variant allele and was associated with decreased OHT sulfating activity. These observations may be related to inter-individual variations of OHT pharmacokinetics and the pharmacologic effects of tamoxifen seen in Japanese patients with breast cancer. (c) 2006 Published by Elsevier B.V.