Raftogianis R B, Wood T C, Otterness D M, Van Loon J A, Weinshilboum R M
Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, Minnesota 55905, USA.
Biochem Biophys Res Commun. 1997 Oct 9;239(1):298-304. doi: 10.1006/bbrc.1997.7466.
The phenol sulfotransferases (PSTs) catalyze the sulfation of both small planar phenols and phenolic monoamines. Three highly homologous PST genes, SULT1A1, SULT1A2, and SULT1A3, are known to exist in humans. The prototypic biochemical phenotype associated with the enzyme encoded by SULT1A1 is the thermal stable (TS) sulfation of 4 microM 4-nitrophenol (TS PST activity). Biochemical pharmacogenetic studies have demonstrated that individual variation in both TS PST activity and thermal stability in humans are inherited. As a step toward understanding molecular mechanisms responsible for the genetic regulation of PSTs in humans, we report here common SULT1A1 nucleotide polymorphisms that are associated with phenotypic variation in both platelet TS PST activity and thermal stability. When 905 human subjects were phenotyped for platelet TS PST activity and thermal stability, activity varied more than 50-fold, and thermal stability varied over 10-fold. DNA was isolated from the blood of 33 of these subjects selected on the basis of "extreme" TS PST phenotypes: high activity and high thermal stability; low activity and low thermal stability; or low activity and high thermal stability. These 33 subjects were genotyped for SULT1A1 by PCR amplification and sequencing of the entire open reading frame (ORF) as well as approximately 1 kb of intron DNA sequence. One common allele, SULT1A12, was uniformly associated with both very low TS PST activity and low thermal stability. The allele frequency of SULT1A12 in a randomly selected population sample of 150 Caucasian blood donors was 0.31 (31%), indicating that approximately 9% of this population would be homozygous for that allele.
酚磺基转移酶（PSTs）催化小分子平面酚类和酚类单胺的硫酸化反应。已知人类存在三个高度同源的PST基因，即SULT1A1、SULT1A2和SULT1A3。与SULT1A1编码的酶相关的典型生化表型是4微摩尔4-硝基苯酚的热稳定（TS）硫酸化反应（TS PST活性）。生化药物遗传学研究表明，人类TS PST活性和热稳定性的个体差异是可遗传的。作为了解人类PSTs遗传调控分子机制的第一步，我们在此报告与血小板TS PST活性和热稳定性表型变异相关的常见SULT1A1核苷酸多态性。当对905名人类受试者的血小板TS PST活性和热稳定性进行表型分析时，活性变化超过50倍，热稳定性变化超过10倍。从这些受试者中根据“极端”TS PST表型选择了33名受试者的血液中提取DNA：高活性和高热稳定性；低活性和低热稳定性；或低活性和高热稳定性。通过对整个开放阅读框（ORF）以及约1 kb的内含子DNA序列进行PCR扩增和测序，对这33名受试者进行SULT1A1基因分型。一个常见等位基因SULT1A12与极低的TS PST活性和低热稳定性均一致相关。在150名白种人献血者的随机选择人群样本中，SULT1A12的等位基因频率为0.31（31%），这表明该人群中约9%的人该等位基因为纯合子。
