Genetics, Vol 122, 905-914, Copyright © 1989

INVESTIGATIONS

Genetic Polymorphism for Human Platelet Thermostable Phenol Sulfotransferase (TS PST) Activity

R. A. Price, R. S. Spielman, A. L. Lucena, J. A. Van-Loon, B. L. Maidak and R. M. Weinshilboum
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Platelet TS PST basal activity and thermal stability were measured in blood samples from 237 individuals in 50 nuclear families. Significant correlations were found among first degree relatives, confirming the previously reported familial aggregation of TS PST basal activity and thermal stability. Commingling analysis of basal TS PST activity provided evidence for multiple component distributions, and after transformation to remove skewness, segregation analysis supported a major gene hypothesis. For TS PST thermal stability, commingling analysis also provided evidence for multiple component distributions. However, segregation analyses were equivocal with regard to the presence of a major gene for thermal stability, since support for a major gene model depended on skewness. Bivariate commingling analysis, which examined thermal stability by simultaneously considering basal activity and activity after heating, suggested that genotypes, as defined by the inferred component distributions for TS PST activity, differ in thermal stability. A three-allele model is proposed as one hypothesis that may account for the combined results of basal activity and thermal stability. The results of this study indicate that a major gene polymorphism in conjunction with polygenic inheritance plays an important role in the regulation of both level of activity and thermal stability of this important drug-metabolizing enzyme in humans.

This article has been cited by other articles:

				J. A. Williams, T. Andersson, T. B. Andersson, R. Blanchard, M. O. Behm, N. Cohen, T. Edeki, M. Franc, K. M. Hillgren, K. J. Johnson, et al. PhRMA White Paper on ADME Pharmacogenomics J. Clin. Pharmacol., July 1, 2008; 48(7): 849 - 889. [Abstract] [Full Text] [PDF]

				S. J. Hebbring, A. A. Adjei, J. L. Baer, G. D. Jenkins, J. Zhang, J. M. Cunningham, D. J. Schaid, R. M. Weinshilboum, and S. N. Thibodeau Human SULT1A1 gene: copy number differences and functional implications Hum. Mol. Genet., March 1, 2007; 16(5): 463 - 470. [Abstract] [Full Text] [PDF]

				G. Liang, X. Miao, Y. Zhou, W. Tan, and D. Lin A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking Carcinogenesis, May 1, 2004; 25(5): 773 - 778. [Abstract] [Full Text] [PDF]

				C. A. Strott Sulfonation and Molecular Action Endocr. Rev., October 1, 2002; 23(5): 703 - 732. [Abstract] [Full Text] [PDF]

				M. W. H. Coughtrie and L. E. Johnston Interactions between Dietary Chemicals and Human Sulfotransferases{---}Molecular Mechanisms and Clinical Significance Drug Metab. Dispos., April 1, 2001; 29(4): 522 - 528. [Abstract] [Full Text]

				W. Zheng, D. Xie, J. R. Cerhan, T. A. Sellers, W. Wen, and A. R. Folsom Sulfotransferase 1A1 Polymorphism, Endogenous Estrogen Exposure, Well-done Meat Intake, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2001; 10(2): 89 - 94. [Abstract] [Full Text]

				R. Raftogianis, C. Creveling, R. Weinshilboum, and J. Weisz Chapter 6: Estrogen Metabolism by Conjugation J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 113 - 124. [Abstract] [Full Text] [PDF]

				N. J Schork, D. B Allison, and B. Thiel Mixture distributions in human genetics research Statistical Methods in Medical Research, June 1, 1996; 5(2): 155 - 178. [Abstract] [PDF]