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

Abstract

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 1860pmol sulfated/h/mg platelet protein (260+/-241pmol sulfated/h/mg platelet protein, median+/-S.D.) using OHT as a substrate. The median values in subjects with SULT*1/*2 (221+/-113pmol sulfated/h/mg platelet protein, range 63-442, n=26) and SULT*2/*2 (124+/-66pmol sulfated/h/mg platelet protein, range 74-231, n=4) were significantly lower than that in subjects with SULT*1/*1 (303+/-267pmol 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.

• Authors: Eiko Ohtake, Fumiko Kakihara, Naoko Matsumoto, Shogo Ozawa, Yasuo Ohno, Setsuo Hasegawa, Hiroshi Suzuki, Takahiro Kubota
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 28 Issue 4 Pg. 272-7 (Jul 2006) ISSN: 0928-0987 [Print] Netherlands
• PMID: 16621480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tamoxifen
• afimoxifene
• Arylsulfotransferase
• SULT1A1 protein, human

Topics

• Adult
• Aged
• Arylsulfotransferase (genetics, metabolism)
• Blood Platelets (enzymology)
• Female
• Gene Frequency
• Genotype
• Humans
• Japan
• Kinetics
• Male
• Middle Aged
• Mutation
• Phenotype
• Tamoxifen (analogs & derivatives, metabolism)