EXPERIMENTAL AND CLINICAL PHARMACOGENETICS

在未来一年，我们建议：a）扩大和进一步发展我们的 遗传药理学书目数据库 密歇根终端计算机系统; B）继续开发方法， 影响个体遗传因素的鉴定和调查 白细胞中抗心律失常药物普萘洛尔的摄取差异 来源于人类和动物模型; c）继续开发高和 低乙酰化同类系小鼠，并继续乙酰化表型 确定来自A/J和 C57 BL/6 J小鼠。 我们还计划探索与性别有关的差异的基础， 肝外（例如，肾）Na-乙酰转移酶在这些小鼠品系和 雄激素不敏感（Tfm）小鼠。 脱乙酰酶活性变异的研究概况 在近交系小鼠品系中的遗传研究也将继续进行， 脱乙酰酶变体的模式随后将在选定的 近交系小鼠 对近交系仓鼠的研究将继续进行， 研究遗传方式和药理毒理学 遗传性N-乙酰基转移酶差异的意义， 鉴定;和d）继续纯化和生物化学表征 人芳基酯酶，并进一步测试人芳基酯酶的两个等位基因假设。 芳基酯酶在人类家族谱系中的差异。

In the coming year we propose: a) to expand and further develop our computerized pharmacogenetic bibliographic data base on the University of Michigan Terminal Computer System; b) to continue to develop methodologies for identification and investigation of genetic factors which affect individual differences in the uptake of the antiarrhythmic drug, propranolol in leukocytes derived from humans and from animal models; c) to continue to develop high and low acetylator congenic strains of mice, and to continue acetylator phenotype determination of recombinant inbred strains of mice derived from A/J and C57BL/6J mice. We also plan to explore the basis for sex-related differences in extrahepatic (e.g., kidney) Na-acetyltransferase in these mouse strains and in androgen-insensitive (Tfm) mice. Survey of deacetylases activity for variation in inbred mouse strains will also be continued and a study of inheritance patterns of deacetylase variants will subsequently be undertaken in selected inbred mouse strains. Studies on inbred hamsters will be continued to investigate the inheritance pattern and pharmacological-toxicological significance of heritable N-acetyltransferase differences which have been identified; and d) to continue purification and biochemical characterization of human arylesterases and to test further the two-allele hypothesis of human arylesterase difference in human family pedigrees.