Polymorphism of debrisoquine hydroxylation among Finns and Lapps.

Arvela, P.; Kirjarinta, M; Kärki, Niilo T.; Pelkonen, Olavi

doi:10.1111/j.1365-2125.1988.tb05301.x

Cited by 13 publications

(2 citation statements)

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“…Except for the lack of lung cancer patients with a PM genotypes, the allelic frequencies in the two populations were quite similar. The percentage of observed PMs in the control population was 3.2%, which fell well within the range obtained previously in Finnish phenotypic studies (20). A PCRbased CYP2D6 genotyping approach similar to ours was applied in a recent study by Daly and co-workers and yielded a good correlation between the debrisoquine metabolic ratio and genotype (21).…”

Section: Resultssupporting

confidence: 88%

Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.

Hirvonen

Husgafvel‐Pursiainen

Anttila

et al. 1993

Environ Health Perspect

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Polymorphism of CYP2D6 gene encoding for debrisoquine hydroxylase was determined genotypically for 94 controls and 77 lung cancer patients using a polymerase chain reaction-based application. Both of the point mutations that give rise to deficient alleles of the CYP2D6 gene are detectable by this method. Out of the 94 healthy controls, 3 individuals (3.2%) had poor metabolizer (PM) genotypes, whereas no PM genotypes were detected in the lung cancer patient group. We observed no difference in the allelic frequencies for either homozygous extensive metabolizers (EMs) or heterozygous EMs between the lung cancer patients and the healthy controls. However, the absence of the poor metabolizer genotype (0/77) in the lung cancer patients is compatible with the hypothesis that there is an increased risk of lung cancer for individuals who are extensive metabolizers of debrisoquine. Another member of the cytochrome P450 gene superfamily that has attracted interest for its potential role in human pulmonary carcinogenesis is the CYPIAI gene. In CYPIAJ gene studies, a polymorphic site assessable to MspI gives rise to two different hybridizable fragments in a Southern blot analysis (alleles Cl and C2, respectively). The C2C2 genotype has previously been associated with an increased risk of lung cancer. So far 74 lung cancer patients, 30 patients with lung diseases other than cancer, and 118 healthy controls have been studied for CYPIAI gene polymorphism. No association between the MspI restriction fragment length polymorphism in the CYPIAJ gene and lung cancer susceptibility has been found.

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Section: Resultssupporting

confidence: 88%

Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.

Hirvonen

Husgafvel‐Pursiainen

Anttila

et al. 1993

Environ Health Perspect

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“…method of Harrison et al (1986). The metabolic ratio was calculated by dividing the % of the dose excreted as debrisoquine by the % excreted as 4-hydroxydebrisoquine (Arvela et al, 1988).…”

Section: Drug Analysismentioning

confidence: 99%

The effects of diltiazem on hepatic drug metabolizing enzymes in man using antipyrine, trimethadione and debrisoquine as model substrates.

Sakai¹,

Kobayashi²,

Hamada³

et al. 1991

Brit J Clinical Pharma

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Six healthy male subjects were given single oral doses of antipyrine (7 mg kg-'), trimethadione (4 mg kg-') and debrisoquine (10 mg) before and during diltiazem treatment (30 mg three times daily orally for 8 days). Antipyrine clearance decreased from 33.7 ± 9.1 to 22.5 ± 4.9 ml min-1 (P < 0.05, mean ± s.e. mean) after diltiazem treatment without any significant change in apparent volume of distribution (0.59 ± 0.06 to 0.60 ± 0.04 1 kg-1), resulting in an increase in antipyrine elimination half-life from 13.4 ± 4.8 to 19.7 ± 3.2 h (P < 0.05). The formation clearance of antipyrine to 4-hydroxyantipyrine was decreased significantly from 10.8 ± 2.7 to 6.6 ± 2.7 ml min-' (P < 0.05), while that to 3-hydroxymethylantipyrine and norantipyrine was not altered by diltiazem. The metabolic ratio of debrisoquine (urinary excretion of debrisoquine/4-hydroxydebrisoquine) was increased significantly from 0.70 ± 0.05 to 1.95 ± 0.20 (P < 0.05), while that of trimethadione (serum concentration of dimethadione/trimethadione) was not changed significantly (0.48 ± 0.08 vs 0.41 ± 0.06) after diltiazem treatment. Diltiazem selectively inhibits cytochrome P-450 isoenzymes.

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Pharmacogenetics of Antidepressant Drug Metabolism and Its Clinical Implications

LLerena¹

2005

Biology of Depression

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Polymorphism of debrisoquine hydroxylation among Finns and Lapps.

Abstract: Debrisoquine hydroxylation polymorphism was studied in 155 Finns and 70 Lapps. The frequency of the poor metabolizer phenotype was 3.2% among Finns (95% confidence interval 0.4-6.0%) and 8.6% among Lapps (95% confidence interval 2.0-15.1%).

Cited by 13 publications

References 11 publications

Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.

Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.

The effects of diltiazem on hepatic drug metabolizing enzymes in man using antipyrine, trimethadione and debrisoquine as model substrates.

Pharmacogenetics of Antidepressant Drug Metabolism and Its Clinical Implications

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