Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects

Abstract

Sulfotransferase (SULT) enzymes catalyze the sulfate conjugation of drugs, other xenobiotics, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in levels of enzyme activity as well as variations in biochemical and physical properties. We set out to compare the frequencies of common SULT1A1 and SULT1A2 alleles in Caucasian, Chinese and African-American subjects. Allele frequencies for SULT1A1*1, *2 and *3 in 242 Caucasian subjects were 0.656, 0.332 and 0.012, respectively. Frequencies of those same alleles were significantly different in 290 Chinese subjects: 0.914, 0.080 and 0.006, respectively, as were frequencies in 70 African-American subjects: 0.477, 0.294 and 0.229, respectively. Ethnic variation in allele frequencies was also observed for SULT1A2, with frequencies in Caucasian subjects for SULT1A2*1, *2 and *3 of 0.507, 0.389 and 0.104; frequencies in Chinese of 0.924 and 0.076 with no *3 alleles observed; and, finally, in African-Americans frequencies of 0.637, 0.249 and 0.114, respectively. We also found that SULT1A1*2 and SULT1A2*2, the most common variant alleles for these two genes, were in positive linkage disequilibrium in all three populations studied, with D' values of 0.776 in Caucasian (P < 0.001), 0.915 in Chinese (P < 0.001) and 0.864 in African-American subjects (P < 0.001). These observations represent a step towards determining the possible functional implications for individual variations in sulfate conjugation of common genetic polymorphisms for SULT1A1 and SULT1A2.