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.

A case–control study on the effect of metabolic gene polymorphisms, nutrition, and their interaction on the risk of non-alcoholic fatty liver disease

“…GSTM1 and GSTT1 null alleles were identified using a multiplex polymerase chain reaction (PCR)-based method (Arand et al 1996). The polymorphic site at nucleotide 638 in exon 7 (Arg213His (*2 allele), rs9282861) of the SULT1A1 gene was genotyped by PCR-restriction fragment length polymorphisms (RFLP) analysis as described by Coughtrie et al (Coughtrie et al 1999), CYP1A1 3 0 -flanking region MspI polymorphism (CYP1A1*2A allele, rs4646903), CYP2E1 PstI polymorphism [CYP2E1*5B allele, rs3813867 (PstI)] and CYP2E1 DraI (*5A or *6 alleles, rs6413432) were also determined by PCR-RFLP analyses. Quality control for each genotyping was performed in each experiment, and 10 % of the total samples were randomly selected and reanalyzed with 100 % concordance.…”

Breast cancer risk associated with genotype polymorphism of the catechol estrogen‐metabolizing genes: A multigenic study on cancer susceptibility

“…26 The PCR primers and extension primers for these 2 SNP were designed using Spectro-Designer software (SEQUENOM, Inc.). A PCR-based RFLP assay 27 was used to determine the SNP of SULT1A1. To genotype deletion polymorphisms in GSTM1 and GSTT1, a multiplex-PCR procedure was used, the primer sets being based on those described previously by Arand et al 28 Our genotyping protocol for the promoter region containing the TA repeats polymorphism of UGT1A1 was similar to that described previously, 23 using an ABI Prism 3100 DNA sequencer and GE-NESCAN3.1 and GENOTYPER 3.7 software.…”

Biological Monitoring of Bisphenol A in a Korean Population

“…PCR amplifications and RFLP analyses were performed as described by Coughtrie et al (1999) with minor modification. Forward and reverse primers were 5Ј-gttggctctgcagggtctctagga-3Ј and 5Ј-cccaaacccccgtactggccagcaccc-3Ј, respectively.…”