Bechtel Y C, Bonaiti-Pellie C, Poisson N, Magnette J, Bechtel P R
Service de Pharmacologie Clinique, CHU Jean Minjoz, Besançon, France.
Clin Pharmacol Ther. 1993 Aug;54(2):134-41. doi: 10.1038/clpt.1993.124.
Population and family studies were undertaken to validate caffeine as a probe drug to establish the genetic status of rapid acetylators and slow acetylators. The acetylator status was established from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine (AFMU/1X) after oral administration of caffeine. We confirmed a bimodal distribution (chi 2(1) = 229.48; p << 10(-9)) of the AFMU/1X ratio in 245 unrelated subjects. A third distribution did not significantly improve the fit to the data (chi 2(1) = 0.04; p = 0.84). Complex segregation analysis of 76 nuclear families confirmed the monogenic inheritance of N-acetyltransferase, with incomplete dominance of the rapid allele over the slow one. We observed a slight shift between the mean activities of heterozygous and homozygous rapid acetylators (t = 2.89; p < 0.01). However, the 30 obligate heterozygotes belonging to the 76 families were evenly distributed among the rapid acetylators and never located in a hypothetic intermediary group between slow acetylators and rapid acetylators.
开展了人群和家庭研究，以验证咖啡因作为一种探针药物来确定快速乙酰化者和慢速乙酰化者的遗传状态。乙酰化状态是通过口服咖啡因后尿液中5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶与1-甲基黄嘌呤的代谢比值（AFMU/1X）来确定的。我们在245名无亲属关系的受试者中证实了AFMU/1X比值呈双峰分布（卡方(1)=229.48；p << 10(-9)）。第三种分布并未显著改善数据拟合度（卡方(1)=0.04；p = 0.84）。对76个核心家庭进行的复杂分离分析证实了N-乙酰转移酶的单基因遗传，快速等位基因对慢速等位基因呈不完全显性。我们观察到杂合子和纯合子快速乙酰化者的平均活性之间有轻微差异（t = 2.89；p < 0.01）。然而，属于这76个家庭的30名必然杂合子在快速乙酰化者中均匀分布，从未出现在慢速乙酰化者和快速乙酰化者之间假设的中间组中。
