Price R A, Cox N J, Spielman R S, Van Loon J A, Maidak B L, Weinshilboum R M
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104.
Genet Epidemiol. 1988;5(1):1-15. doi: 10.1002/gepi.1370050102.
Sulfate conjugation is an important pathway in the biotransformation of drugs and neurotransmitters. The thermolabile (TL) form of the enzyme phenol sulfotransferase (PST) catalyzes the sulfation of catecholamine neurotransmitters and drugs such as methyldopa and acetaminophen. Platelet TL PST activity was measured in blood samples from 232 individuals in 49 nuclear families. Correlations ranged from 0.43 to 0.45 for parent-offspring pairs and from 0.44 to 0.47 for siblings. Mother-father correlations were not significantly different from zero. Although evidence was not unequivocal, both segregation and commingling analyses provided some support for a major gene influence on TL PST activity, with other variation due to polygenic background. In both sets of analyses, however, support for a major gene hypothesis depended upon skewness in the TL PST activity distribution. A polygenic model with high heritability (0.77) was most strongly supported with the log transformed data. These results confirm and extend a previous report of high heritability of TL PST based on a study of twins. In addition, our results raise the possibility of a major gene effect on this important catecholamine- and drug-metabolizing enzyme--a possibility that can now be evaluated using biochemical techniques.
硫酸化结合是药物和神经递质生物转化的一条重要途径。酚磺基转移酶（PST）的热不稳定（TL）形式催化儿茶酚胺神经递质以及甲基多巴和对乙酰氨基酚等药物的硫酸化反应。在49个核心家庭的232名个体的血样中测量了血小板TL PST活性。亲子对之间的相关性在0.43至0.45之间，兄弟姐妹之间的相关性在0.44至0.47之间。父母之间的相关性与零无显著差异。尽管证据并不明确，但分离分析和混合分析都为主要基因对TL PST活性的影响提供了一些支持，其他变异则归因于多基因背景。然而，在两组分析中，对主要基因假说的支持都依赖于TL PST活性分布的偏态性。对数转换数据最有力地支持了具有高遗传力（0.77）的多基因模型。这些结果证实并扩展了先前基于双胞胎研究得出的TL PST具有高遗传力的报告。此外，我们的结果增加了主要基因对这种重要的儿茶酚胺和药物代谢酶产生影响的可能性——现在可以使用生化技术对这一可能性进行评估。
