Acetylator polymorphism in rheumatoid arthritis

Ladero, J. M.; Andres, M. P.; Bañares, A; Fernández, B. Malvar; Hernández, César Arranz; Benı́tez, Julio

doi:10.1007/bf00315397

Cited by 10 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous human epidemiological studies have suggested an association between rapid acetylator phenotype and colorectal cancer (Lang et al 1986;Ilett et al 1987;Wohlleb et al 1990), whereas a previous study from our laboratory (Kirlin et al 1991) and others (Roots et al 1989;Ladero et al 1991) did not find this association. Our data comparing NAT2 allelic frequencies showed virtually identical distributions of the M1, M2, M3, and WT alleles between the non-cancer and colorectal cancer groups.…”

Section: Discussioncontrasting

confidence: 60%

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

et al. 1993

View full text Add to dashboard Cite

Polymorphic expression of arylamine N-acetyltransferase (EC 2.3.1.5) may be a differential risk factor in metabolic activation of arylamine carcinogens and susceptibility to cancers related to arylamine exposures. Human epidemiological studies suggest that rapid acetylator phenotype may be associated with higher incidences of colorectal cancer. We used restriction fragment length polymorphism analysis to determine acetylator genotypes of 44 subjects with colorectal cancer and 28 non-cancer subjects of similar ethnic background (i.e., approximately 25% Black and 75% White). The polymorphic N-acetyltransferase gene (NAT2) was amplified by the polymerase chain reaction from DNA templates derived from human colons of colorectal and non-cancer subjects. No significant differences in NAT2 allelic frequencies (i.e., WT, M1, M2, M3 alleles) or in acetylator genotypes were found between the colorectal cancer and non-cancer groups. No significant differences in NAT2 allelic frequencies were observed between Whites and Blacks or between males and females. Cytosolic preparations from the human colons were tested for expression of arylamine N-acetyltransferase activity. Although N-acetyltransferase activity was expressed for each of the arylamines tested (i. e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, beta-naphthylamine), no correlation was observed between acetylator genotype and expression of human colon arylamine N-acetyltransferase activity. Similarly, no correlation was observed between subject age and expression of human colon arylamine N-acetyltransferase activity. These results suggest that arylamine N-acetyltransferase activity expressed in human colon is catalyzed predominantly by NAT1, an arylamine N-acetyltransferase that is not regulated by NAT2 acetylator genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussioncontrasting

confidence: 60%

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

et al. 1993

View full text Add to dashboard Cite

show abstract

“…As the slow acetylator phenotype predominates in Caucasian populations, the excess of rapid acetylators among RA patients (55.7%) found in this study suggested a possible relation of the disease with this phenotype. Two other phenotyping studies, including a fewer number of patients, agreed with this preliminary conclusion [26,27]. However, genotyping methods have not definitely solved this issue.…”

Section: Rheumatoid Arthritis (Ra)supporting

confidence: 60%

Influence of Polymorphic N-Acetyltransferases on Non-Malignant Spontaneous Disorders and on Response to Drugs

2008

CDM

View full text Add to dashboard Cite

Polymorphic N-acetyl transferases (NAT) 1 and 2 are involved in detoxification of xenobiotic arylamines and hydralazines. These common environmental chemicals may be related to the pathogenesis of many spontaneous disorders, mainly malignancies, but also disimmune or degenerative diseases, for which a polygenic predisposition has been suggested. Hence, polymorphic NAT genes (NAT2 has been the most studied one) may be low-penetrance risk genes for some of these disorders. Although a relation of risk may be definitely discarded for systemic lupus erythematosus (SLE), inflammatory bowel disease and endometriosis, more research is needed for rheumatoid arthritis, Parkinson's, Alzheimer's, Behçet's and periodontal diseases , as current results are inconclusive but suggest a possible relation with NAT2 polymorphism. In diabetes mellitus the possible relation with the rapid phenotype may be due to acquired metabolic changes and more genotyping studies are needed. NAT2 slow metabolizers are more prone to the side effects of polymorphically acetylated drugs, as is the SLE-like syndrome induced by hydralazine and procainamide, the side effects due to sulphasalazine and the skin rash secondary to many sulphonamides. Future research should be based on well-designed studies, with adequate sample sizes and homogeneous recruitment criteria, to obviate the proliferation of small studies that are time- and resource-consuming without offering definite answers.

show abstract

“…Two of three reports on human colorectal cancer, (13,28,29) have found that rapid acetylators are overrepresented among cases as compared to controls. In this context, we have shown that the heterocyclic amines, which have been implicated as a risk factor in this disease, are poor substrates for N-acetylation in human liver; however, they readily undergo hepatic N-oxidation and subsequent N-glucuronidation (vide infra), resulting in conjugated N-hydroxy metabolites that can be transported to the colonic lumen, hydrolyzed by ,B-glucuronidases, and reabsorbed.…”

Section: Acetyltransferasesmentioning

confidence: 99%

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Kadlubar¹,

Butler²,

Kaderlik³

et al. 1992

Environmental Health Perspectives

View full text Add to dashboard Cite

The metabolic pathways associated with carcinogenic aromatic amines in humans provide an excellent example of polymorphisms that appear to be relevant to human carcinogenesis. In this regard, the N-acetylation of arylamines and the O-acetylation of their N-hydroxy metabolites are catalyzed preferentially by a genetically polymorphic acetyltransferase, high activity of which has been correlated with decreased risk for urinary bladder cancer and increased susceptibility to colorectal cancer. Cytochrome P450IA2, the principal liver enzyme involved in aromatic amine N-oxidation, exhibits a wide interindividual variation that appears trimodal in several populations and is clearly inducible by cigarette smoking and probably other host factors as well. UDP-Glucuronosyltransferases, which catalyze the N-glucuronidation of N-hydroxyarylamines and are likely to be responsible for their transport to the colon, show widely varied but unimodal distributions in humans. In contrast, human liver sulfotransferase activity forN-hydroxyarylamines, which would be expected to decrease their transport through the circulation, is catalyzed by a polymorphic enzyme(s) that is expressed at higher levels in blacks, as compared to whites, and could contribute to their relatively lower incidence of urinary bladder cancer. Peroxidative activation of aromatic amines can also occur, especially from prostaglandin H synthase in the urinary bladder and myeloperoxidase in the lungs of cigarette smokers, and both show considerable individual variability, apparently due to the extent of tissue inflammation. In a pilot study, we have examined two of these polymorphisms, acetyltransferase and cytochrome P450IA2, in colorectal cancer/ polyp cases (n = 38) and controls (n = 100) and found that individuals who are both rapid acetylators and rapid N-oxidizers are indeed more prevalent (p < 0.008) among cases (37%) than among controls (16%).

show abstract

Acetylator polymorphism in rheumatoid arthritis

Cited by 10 publications

References 9 publications

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

Influence of Polymorphic N-Acetyltransferases on Non-Malignant Spontaneous Disorders and on Response to Drugs

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Contact Info

Product

Resources

About