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 Arg (213) to His exchange and eliminates a Bsp143II restriction site. SULT1A1*H is shows lower enzyme activity and thermostability than SULT1A1*Arg, In SUL T1A2, an A to C transversion causes an Asn(235) to Thr exchange and introdu ces a BpiI restriction site. Enzyme SULT1A2*Thr is less active than SULT1A2 *Asn. These substitutions were detected by restriction fragment length poly morphism analyses of genomic sequences amplified by polymerase chain reacti on. Despite the high similarity between the different human SULT1A genes, i t was possible to amplify specifically the polymorphic parts of either SULT 1A1 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 subject s was analysed. Allele frequencies were 0.63 and 0.37 for SULT1A1*Arg and * His, and 0.62 and 0.38 for SULT1A2*Asn and *Thr, respectively. The frequenc y of the haplotype SULT1A1* Aug/SULT1A2*Asn (0.61) was nearly as high as th e allele frequencies of its components. The same was observed for the haplo type SULT1A1* His/SULT1A2*Thr, whose frequency was 0.35. In contrast, haplo types 1A1*Arg/1A2*Thr and 1A1*His/1A2*Asn were very rare. Their frequencies (0.02 each) were less than 10% of the figures expected in an independent d istribution. The results demonstrate a strong association of the alleles pr oducing the more active enzyme variants (SULT1A1*Arg and SULT1A2*Asn) and o f those encoding the less active variants (SULT1A1*His and SULT1A2*Thr), Ph armacogenetics 10:163-169 (C) 2000 Lippincott Williams & Wilkins.