Association between functional genetic polymorphisms of human sulfotransferases 1A1 and 1A2.

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).