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Acetylator phenotype and genotype in patients infected with HIV: discordance between methods for phenotype determination and genotype.

机译:HIV感染患者的乙酰化剂表型和基因型:表型测定方法和基因型之间的不一致。

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The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data.
机译:将患有和不患有急性疾病的AIDS患者的乙酰化剂表型和基因型与健康对照组的进行比较(每组30个)。使用两种探针药物,咖啡因和氨苯砜来确定急性病队列中的表型。聚合酶链反应扩增和限制性片段长度多态性分析用于区分26个已知的NAT2等位基因和21个最常见的NAT1等位基因。在急性病的AIDS患者中发现的慢速:快速乙酰化剂表型的分布(%)与所使用的探针底物不同:咖啡因为70:30,氨苯砜为53:47。两种方法之间的表型分配差异很大,并且表型和基因型之间存在许多差异。 NAT2基因型分布为45:55慢速:快速。仅用咖啡因表型的对照受试者在基因型上为慢速:快速67:33,而速比为60:40。仅使用氨苯砜表型的稳定AIDS患者在基因型上慢速:快速:55:45,慢速:46:54。解决了急性感染后,对12名急性病患者进行了氨苯砜表型分析。在所有情况下,表型分配均保持不变。在所有三个组中,NAT1等位基因的分布均相似。从咖啡因表型与氨苯砜表型或基因型之间的不一致程度可以明显看出,在急性病患者中使用咖啡因作为NAT2的探针时应谨慎行事。同样清楚的是,对乙酰化多态性的有意义的研究需要表型和基因型数据。

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