Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity.
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.
Price
R A
RA
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104.
Spielman
R S
RS
Lucena
A L
AL
Van Loon
J A
JA
Maidak
B L
BL
Weinshilboum
R M
RM
D000293:Adolescent; D000328:Adult; D000375:Aging; D000704:Analysis of Variance; D015239:Arylsulfotransferase / Q000097:blood / Q000235:genetics*; D001481:Basal Metabolism; D001792:Blood Platelets / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D004795:Enzyme Stability; D005190:Family; D005260:Female; D005838:Genotype; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic
D015239:Arylsulfotransferase