Phenol Sulfotransferase Pharmacogenetics in Humans: Association of CommonSULT1A1Alleles with TS PST Phenotype

Raftogianis, Rebecca B.; Wood, Thomas O.; Otterness, Diane M.; Loon, Jon A. Van; Weinshilboum, Richard M.

doi:10.1006/bbrc.1997.7466

Cited by 281 publications

(228 citation statements)

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“…These were: (i) Val108Met in COMT (resulting from a G-to-A transition); the Met allele encodes a heat-sensitive form of COMT and is defined as the slow activity allele 21 ; (ii) Arg213His in SULT1A1 (resulting from a G-to-A transition); the His allele was found to be associated with low thermal stability and low SULT activity in an in vitro study; 22 and (iii) the repeat number polymorphism in the A(TA)nTAA motif of the TATA box in the promoter region of UGT1A1; functional analyses of the transcriptional activity have shown that the transcription activation of this gene is correlated inversely with repeat number, and alleles with 7 or 8 repeats show low expression 23 ; (iv) the T-to-C transition leading to replacement of Val with Ala in the mitochondrial targeting sequence of MnSOD; the resulting amino acid change is predicted to alter the secondary structure of the protein and may affect the cellular allocation and mitochondrial transport of this anti-oxidative enzyme 24 ; (v) genetic deletion polymorphisms of GSTM1 and GSTT1; the deleted alleles result in no enzyme activity. 25 The single nucleotide polymorphisms (SNP) of COMT and MnSOD were genotyped by a MassARRAY system (SEQUE-NOM, Inc., San Diego, CA), based on the primer extension protocol.…”

Section: Genotypic Polymorphism and Genotypingmentioning

confidence: 99%

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

Cheng

Chen

Huang

et al. 2004

Intl Journal of Cancer

102

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Estrogen has been suggested to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we carried out a multigenic case-control study of 469 incident breast cancer patients and 740 healthy controls to define the role of important genes involved in the different metabolic steps that protect against the potentially harmful effects of CE metabolism. We studied the 3 genes involved in CE detoxification by conjugation reactions involving methylation (catechol-O-methyltransferase, COMT), sulfation (sulfotransferase 1A1, SULT1A1), or glucuronidation (UDP-glucuronosyltransferase 1A1, UGT1A1), one (manganese superoxide dismutase, MnSOD) involved in protection against reactive oxidative species-mediated oxidation during the conversion of CEsemiquinone (CE-SQ) to CE-quinone (CE-Q), and 2 of the glutathione S-transferase superfamily, GSTM1 and GSTT1, involved in CE-Q metabolism. Support for this hypothesis came from the observations that (i) there was a trend toward an increased risk of breast cancer in women harboring a greater number of putative high-risk genotypes of these genes (p < 0.05); (ii) this association was stronger and more significant in those women who were more susceptible to estrogen [no history of pregnancy or older (>26 years) at first full-term pregnancy (FFTP)]; and (iii) the risks associated with having one or more high-risk genotypes were not the same in women having experienced different menarche-to-FFTP intervals, being more significant in women having been exposed to estrogen for a longer period (>12 years) before FFTP. Furthermore, because CE-Q can attack DNA, leading to the formation of double-strand breaks (DSB), we examined whether the relationship between cancer risk and the genotypic polymorphism of CE-metabolizing genes was modified by the genotypes of DSB repair genes, and found that a joint effect of CE-metabolizing genes and one of the two DSB repair pathways, the homologous recombination pathway, was significantly associated with breast cancer development. Based on comprehensive CE metabolizing gene profiles, our study provides support to the hypotheses that breast cancer can be initiated by estrogen exposure and that increased estrogen exposure confers a higher risk of breast cancer by causing DSB to DNA.Key words: breast cancer; estrogen; catechol estrogen; polymorphism; molecular epidemiology An increased risk of breast cancer due to prolonged exposure to estrogen has been well documented by epidemiological observations showing that estrogen-related risk factors, including age at menarche, age at menopause, parity and age at first full-term pregnancy (FFTP), are significantly associated with breast cancer risk. 1,2 Why estrogen exposure should increase breast cancer risk is an intriguing question that has not been conclusively answered. One simple explanation is that the proliferative effect of estrogen on breast epithelium promotes the growth of tumor cells, leading to progression of breast cancer. [3...

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Section: Genotypic Polymorphism and Genotypingmentioning

confidence: 99%

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

Cheng

Chen

Huang

et al. 2004

Intl Journal of Cancer

102

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“…The phenol family is further subdivided into the phenol and oestrogen subfamilies. Of the human enzymes, there are phenolic sulfotransferases (SULT1A1, 1A2 and 1A3), an oestrogen sulfotransferase (SULT1E1) and hydroxysteroid sulfotransferases (SULT2A1 and 2B1) Raftogianis et al 1997;Her et al 1998).…”

Section: Sulfationmentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

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“…Among phase II enzymes, sulfotransferases (SULTs) and uridine diphosphate glucuronosyltransferases (UGTs) are known to be involved in BPA metabolism (Elsby et al 2001;Yokota et al 1999;Suiko et al 2000;Raftogianis et al 1997). Among SULTs, SULT1A1 is thought to sulfate phenolic compounds like BPA, and is considered to be genetically polymorphic (Raftogianis et al 1997;Nowell et al 2000;Carlini et al 2001) in human. There are four known different alleles in SULT1A1, and are reported as: SULT1A1*1, SULT1A1*2, SULT1A1*3, and SULT1A1*4 in the literature.…”

Section: Introductionmentioning

confidence: 99%

“…Toxicol. 44, 546 -551 (2003) DOI: 10.1007/s00244-002-2124 A R C H I V E S O F Environmental Contamination a n d Toxicology transition results in an Arg 213 to His alteration in the amino acid sequence and leads to lower enzyme activity in people with SULT1A1*2 than in people with SULT1A1*1 (Raftogianis et al 1997;Nowell et al 2000;Carlini et al 2001). Thus, urinary BPA levels can be affected by the genetic polymorphism of SULT1A1.…”

Section: Introductionmentioning

confidence: 99%

Biological Monitoring of Bisphenol A in a Korean Population

Yang

Kim

Lee

et al. 2003

Archives of Environmental Contamination and Toxicology

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Abstract.To conduct proper biological monitoring of environmental exposure to bisphenol A (BPA), the variation in host susceptibility need to be investigated. For this purpose, we studied effects of genetic polymorphism in sulfotransferase (SULT) 1A1 on urinary BPA, a biomarker for BPA exposure, in 73 Koreans (male, 34; female, 39; age, 48.9 Ϯ 11.9 yrs). We used reverse phase-HPLC/FD for analysis of urinary BPA and obtained information from each subject on lifestyle, environment, and potential exposure to BPA via food. The HPLC/FD method showed good reproducibility (CVs Ͻ 0.1) and a relatively sensitive detection limit of 0.012 g/L. These methods yielded a geometric mean of urinary BPA as 9.54 g/L (8.91 g/g creatinine), with a geometric standard deviation of 8.32 g/L. Among potential routes for BPA exposure, only "vinyl wrapping of microwave heating" indicated a borderline positive association with urinary BPA level ( p ϭ 0

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Phenol Sulfotransferase Pharmacogenetics in Humans: Association of CommonSULT1A1Alleles with TS PST Phenotype

Cited by 281 publications

References 0 publications

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

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

Neonatal Hepatic Drug Elimination

Biological Monitoring of Bisphenol A in a Korean Population

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