Further evidence for the lack of association between acetylator phenotype and systemic lupus erythematosus

Baer, Alan N.; Woosley, Raymond L.; Pincus, Theodore

doi:10.1002/art.1780290408

Cited by 22 publications

(6 citation statements)

References 30 publications

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“…This observation led to the hypothesis that idiopathic SLE might develop, particularly in the slow acetylator, in response to exposure to environmental amines (35). In a series of 64 SLE patients studied at our institution, we observed a distribution of acetylator phenotypes that was comparable with that in control groups consisting of healthy volunteers and of medical service patients without SLE (9). We therefore could not confirm the suggestion by others that there is an excess of slow acetylators among patients with idiopathic SLE (35).…”

Section: Discussioncontrasting

confidence: 73%

“…tors seen in this population was greater than that observed in a control population studied at our institutim (9), but these differences were not statistically significant. This difference in distribution of acetylator phenotypes was not as marked in a larger study that…”

Section: Analysis Of Debrisoquine Metabolic Ratios In Slecontrasting

confidence: 73%

“…Forty-two unrelated patients with SLE underwent determination of their debrisoquine oxidation phenotype. Thirty-nine of these patients also underwent determination of their dapsone acetylator phenotype and are included in a separare report of acetylator phenotype in SLE (9). All 42 patients met 4 or more of the American Rheumatism Association criteria for the classification of SLE (10).…”

Section: Methodsmentioning

confidence: 99%

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Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

Baer

McAllister

Wilkinson

et al. 1986

Arthritis & Rheumatism

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Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydraxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metaibolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metalbolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P < 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metalbolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE. ~~Presented in part at the Southeastern Regional Meeting of the American Rheumatism Association, Baltimore, Maryland, December 7, 1984, and Recent reports suggest that genetic differences in oxidative metabolism are potentially important in the pathogenesis of systemic lupus erythematosus (SLE). Lahita and coworkers (1-3) have provided evidence that SLE patients differ from normal subjects in their patterns of oxidative metabolism of estradiol and testosterone. Drayer et a1 (4) demonstrated that the rate of hydroxylation, as measured by pentobarbital elimination, is increased in SLE patients, as compared with normal controls. Differences in patterns of oxidative metabolism could determine the likelihood of activating drugs or environmental chemicals to toxic metabolites that could be pathogenic in SLE. Further, pathways of oxidative metabolism could influence the metabolism of sex steroid hormones or other endogenous substrates that are known to modulate the activity of experimental SLE.The antihypertensive agent, debrisoquine, provides a useful probe to analyze patterns of xenobiotic oxidation in patients with idiopathic SLE. The pharmacology of this post-ganglionic blocking agent is notable for marked inter-patient variation in response to a given dose. In 1977, Mahgoub et a1 ( 5 ) demonstrated that the extent of metabolism of this drug to its principal and pharmacologically inactive metabolite, 4-hydroxydebrisoquine (Figure l), is genetically determined. In family studies, the impaired ability to form the 4-hydroxydebrisoquine metabolite was found to be inherited as an autosomal recessive trait (5). Two phenotypes have been identified in population studies: the "extensive metabolizer" phenotype, comprising individuals who are either homozygous or heterozygous with respect to the dominant allele and who constitute approximately 92% of British and American white populations; and the "poor metabolizer" phe-

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Section: Discussioncontrasting

confidence: 73%

Section: Analysis Of Debrisoquine Metabolic Ratios In Slecontrasting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

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Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

Baer

McAllister

Wilkinson

et al. 1986

Arthritis & Rheumatism

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“…Although there are con¯icting results with respect to the association of NAT2-acetylation status and risk of developing SLE [9,19], there is some evidence that NAT2-acetylation polymorphism has been linked to susceptibility to certain autoimmune diseases [8,9,10]. An overrepresentation of NAT2 slow acetylators was found among patients with SLE [8,9].…”

Section: Discussionmentioning

confidence: 96%

N-acetyltransferase polymorphism in patients with Behçet's disease

Aynacioglu

Bozkurt

Nacak

et al. 2001

Eur J Clin Pharmacol

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“…The presence of mutation in both alleles of NAT2 is manifested by the free acetylation phenotype (slow acetylator). 4,16 Although there are conflicting results with respect to the association of NAT2-acetylation status and risk of developing SLE, 7,17 there is some evidence that NAT2acetylation polymorphism has been linked to susceptibility to certain autoimmune diseases. [8][9][10] Behcet's disease is suggested to be a systemic inflammatory disorder like SLE.…”

Section: Discussionmentioning

confidence: 99%

N-acetyltransferase 2 polymorphisms in patients with Behcet's disease

Tamer¹,

Türsen²,

Eskandari³

et al. 2005

Clin Exp Dermatol

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It is possible that dietary, environmental factors and/or genetic polymorphisms in xenobiotic-metabolizing enzymes may contribute to the development of Behcet's disease. As N-acetyltransferase (NAT) 2 is an important xenobiotic-metabolizing enzyme and theoretically the nonacetylated xenobiotics may induce an autoimmune mechanism, the aim of the present study was to investigate whether the genetic polymorphism of NAT2 plays a role in susceptibility to Behcet's disease. Forty Behcet's disease patients and 82 control subjects were enrolled in the study. NAT2*5A, NAT2*6A, NAT27*A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). The NAT2*5A and NAT2*6A mutant genotypes carried an increased risk of developing Behcet's disease [odds ratio (OR) = 66.29, 95% confidence interval (CI) = 8.21-535.33; and OR = 24; 95% CI = 2.04-304.98, respectively]. The NAT2*7A/B and NAT2*14A gene polymorphisms were not an increased risk for developing Behcet's disease. As a result of this study we conclude the NAT2 slow acetylator status may be a determinant in susceptibility to Behcet's disease. This finding may have implications for the theories of the pathogenesis of the disease as well as for therapeutic aspects.

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Further evidence for the lack of association between acetylator phenotype and systemic lupus erythematosus

Cited by 22 publications

References 30 publications

Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

N-acetyltransferase polymorphism in patients with Behçet's disease

N-acetyltransferase 2 polymorphisms in patients with Behcet's disease

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