Engelke C E, Meinl W, Boeing H, Glatt H
Department of Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke.
Pharmacogenetics. 2000 Mar;10(2):163-9. doi: 10.1097/00008571-200003000-00008.
Three human phenol sulfotransferases, provisionally named SULT1A1, 1A2 and 1A3, show 91-96% homology of their amino acid sequences and are encoded by neighbouring gene loci. Functional genetic polymorphisms are known for two of these sulfotransferases. In SULT1A1, a G to A transition leads to an Arg213 to His exchange and eliminates a Bsp143II restriction site. SULT1A1His shows lower enzyme activity and thermostability than SULT1A1Arg. In SULT1A2, an A to C transversion causes an Asn235 to Thr exchange and introduces a BpiI restriction site. Enzyme SULT1A2Thr is less active than SULT1A2Asn. These substitutions were detected by restriction fragment length polymorphism analyses of genomic sequences amplified by polymerase chain reaction. Despite the high similarity between the different human SULT1A genes, it was possible to amplify specifically the polymorphic parts of either SULT1A1 or 1A2, but not the homologous sequences of the other SULT, by setting the forward primer into intron 6. DNA from 300 adult male Caucasian subjects was analysed. Allele frequencies were 0.63 and 0.37 for SULT1A1Arg and His, and 0.62 and 0.38 for SULT1A2Asn and Thr, respectively. The frequency of the haplotype SULT1A1Arg/SULT1A2Asn (0.61) was nearly as high as the allele frequencies of its components. The same was observed for the haplotype SULT1A1His/SULT1A2Thr, whose frequency was 0.35. In contrast, haplotypes 1A1Arg/1A2Thr and 1A1His/1A2Asn were very rare. Their frequencies (0.02 each) were less than 10% of the figures expected in an independent distribution. The results demonstrate a strong association of the alleles producing the more active enzyme variants (SULT1A1Arg and SULT1A2Asn) and of those encoding the less active variants (SULT1A1His and SULT1A2Thr).
三种人类酚磺基转移酶，暂命名为SULT1A1、1A2和1A3，其氨基酸序列具有91%-96%的同源性，且由相邻的基因座编码。已知其中两种磺基转移酶存在功能基因多态性。在SULT1A1中，G到A的转换导致Arg213被His取代，并消除了一个Bsp143II限制性酶切位点。SULT1A1His的酶活性和热稳定性低于SULT1A1Arg。在SULT1A2中，A到C的颠换导致Asn235被Thr取代，并引入了一个BpiI限制性酶切位点。酶SULT1A2Thr的活性低于SULT1A2Asn。这些取代通过聚合酶链反应扩增的基因组序列的限制性片段长度多态性分析来检测。尽管不同的人类SULT1A基因之间高度相似，但通过将正向引物置于内含子6中，可以特异性扩增SULT1A1或1A2的多态性部分，而不是其他SULT的同源序列。分析了300名成年男性白种人的DNA。SULT1A1Arg和His的等位基因频率分别为0.63和0.37，SULT1A2Asn和Thr的等位基因频率分别为0.62和0.38。单倍型SULT1A1Arg/SULT1A2Asn的频率（0.61）几乎与其组成部分的等位基因频率一样高。单倍型SULT1A1His/SULT1A2Thr的情况也是如此，其频率为0.35。相比之下，单倍型1A1Arg/1A2Thr和1A1His/1A2Asn非常罕见。它们的频率（均为0.02）低于独立分布预期值的10%。结果表明，产生活性较高的酶变体的等位基因（SULT1A1Arg和SULT1A2Asn）与编码活性较低的变体的等位基因（SULT1A1His和SULT1A2Thr）之间存在强关联。
