Phenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations

Abstract

Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is an important component of the body's chemical defence mechanism, but also acts to bioactivate mutagens such as hydroxylated aryl and heterocyclic amines. A major human sulphotransferase, SULT1A1 (P-PST), metabolizes and/or bioactivates many drugs, iodothyronines and hydroxylated aromatic amines. The enzyme activity varies widely within the population and is under genetic control. We have developed an assay detecting a G-->A transition in SULT1A1 that causes an Arg213-->His substitution associated with low SULT activity and altered enzyme properties, and have used it to assess the SULT1A1 genotype in Caucasian (n=293) and African (Nigerian, n=52) populations. We show that the mutant SULT1A1*2 allele is present at frequencies of 0.321 and 0.269 in the Caucasian and African populations respectively. We also demonstrate a significant age-related difference in SULT1A1 genotype within our Caucasian population, with increasing incidence of SULT1A1*1 homozygosity and decreasing incidence of SULT1A1*2 homozygosity with increasing age, indicating a potential association of SULT1A1*1 allozyme(s) with protection against cell and/or tissue damage during aging.

Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer

“…Therefore the presence of normal cells and malignant cells without DNA lesions in the locus of CYP3A5 , CYP2D6 , SULT1A1 and UGT2B15 decreases the risk of genotype misclassification. This is also supported by the fact that allele frequencies of CYP3A5*3 , CYP2D6*1 , SULT1A1*2 and UGT2B15*2 in the current study population are comparable to those reported by others in Caucasian populations [18,19,26,27]. …”

“…The primer sequences used in the PCR of CYP2D6 and SULT1A1 were adopted from Hanioka and colleagues [21] and Coughtrie and colleagues [26], respectively, whereas the CYP3A5 and UGT2B15 genes were amplified with forward (5'-ACCACCCAGCTTAACGAATG-3' and 5'-AGAGCTTGTTCAGAGGGGTCATGAG-3') and reverse (5'-AGCACAGGGAGTTGACCTTC-3' and 5'-AAATTCTCGATAGATGGATATATGG-3') primers, respectively. The following PCR reagents were added to a reaction volume of 20 μl: 2 mM MgCl 2 , 0.2 mM dNTPs, 0.5 unit of Taq DNA polymerase, and 1 μM each of forward and reverse primer in 1 × PCR buffer.…”

Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

“…The CYP2D6 and SULT1A1 genes were amplified with PCR in separate reactions using 30 ng DNA and 60 ng DNA, respectively. The primer sequences used in the PCR of CYP2D6 and SULT1A1 were adopted from Hanioka and colleagues [14] and Coughtrie and colleagues [17]. The following PCR reagents were added to a reaction volume of 20 μl: 2 mM MgCl 2 , 0.2 mM dNTPs, 0.5 units Taq DNA polymerase, and 1 μM each of forward and reverse primer in 1 × PCR buffer.…”

SULT1A1 genotype, active and passive smoking, and breast cancer risk by age 50 years in a German case–control study

“…SULT1A1 -specific primers and hybridization probes were used to detect G638A in exon 7. The primers for DNA amplification were previously described by Coughtrie and coworkers [21]. As sensor and anchor probes, we used LCRed640-CAgggAgCgCCCCACAA-p and gAACCATgAAgTCCACggTCTCCTCT-x, respectively.…”