Genetic Testing for Enzymes of Drug Metabolism: Does It Have Clinical Utility for Pain Medicine at the Present Time? A Structured Review

Fishbain, David A.; Fishbain, Dana; Lewis, John E.; Cutler, Robert; Cole, Brandly; Rosomoff, Hubert L.; Rosomoff, R. Steele

doi:10.1111/j.1526-4637.2004.04007.x

Cited by 32 publications

(52 citation statements)

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“…GSTM1, GSTT1, and GSTP1 are phase II enzymes [4]. Genetic polymorphisms of these enzymes affect individual susceptibility to various pathologies, including cancer [7]. Decreased activity of GSTM1 and GSTT1, because of deletion of the genes, has been reported.…”

Section: Introductionmentioning

confidence: 99%

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

et al. 2008

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Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C --> A, cytochrome p450 2D6 (CYP2D6) 1934 G --> A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70-9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.

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Section: Introductionmentioning

confidence: 99%

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

et al. 2008

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“…Several thorough reviews of drugs and environmental chemicals metabolized by CYP450 enzymes are available [1,4,5,6,7]. Table 1 depicts a selection of CYP450 genes affecting drug metabolism.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 Enzyme Polymorphism Frequency in Indigenous and Native American Populations: A Systematic Review

Jaja

Burke

Thummel

et al. 2008

Public Health Genomics

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Objective: The purpose of our study was to evaluate the evidence on the prevalence of cytochrome P450 enzyme polymorphisms as potential genetic factors influencing drug efficacy and safety in the indigenous populations of the American hemispheres. Methods: We conducted a systematic review of studies published between 1985 and 2006 using the Pubmed database. Results: We identified only 10 original research studies on CYP2A6, CYP2D6, CYP2C9, CYP2C19 and CYP2E1 in 13 indigenous American populations. Interethnic differences in the frequency of CYP450 genetic variants existed both among the examined indigenous populations and in comparison with African, Asian and European populations. Conclusions: There are surprisingly few data on CYP450 enzyme polymorphisms in indigenous American populations, and it is difficult to draw any clear inferences about how these populations might be expected to respond to drugs in relation to other racial or ethnic groups. This lack of information could create a barrier to the use of pharmacogenetic testing in these populations. Collaborative partnerships between indigenous communities and researchers are needed to avail the clinical benefits of CYP450 enzyme polymorphism testing to indigenous populations.

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“…In eq 2, ΔM max is the maximum amount that (2) CYP1B1 can be bound and ΔM max is the characteristics of the sensor surface, which is equivalent to the binding of CYP1B1 when all the scFvs are converted to the CYP1B1-scFv complex. ΔM is the measured CYP1B1 binding amount at equilibrium, which is a function of the CYP1B1 concentration and will not change with the time, and [CYP1B1] is the original concentration of CYP1B1.…”

Section: Binding Affinitymentioning

confidence: 99%

Recombinant Antibody Piezoimmunosensors for the Detection of Cytochrome P450 1B1

et al. 2007

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The phase I enzyme known as cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of many endogenous and exogenous compounds, including carcinogens. CYP1B1 is overexpressed in a wide variety of human diseases ranging from diabetes to malignancies, such as invasive breast cancer. Because of its microsomal location in the cell, CYP1B1 could not be measured directly by existing methods but only assessed indirectly via the determination of the catalytic products. We report here a rapid, sensitive piezoimmunosensor for detection of CYP1B1 using single-chain fragment variable antibodies (scFv) as recognition elements and a quartz crystal microbalance (QCM) as the transducer. Three anti-CYP1B1 scFvs (designated B-66, D-23, and L-21) were biotinylated and used to capture and specifically detect CYP1B1 from samples in solution. ScFvs are smaller than most commonly used antibodies and can be coated onto QCM surfaces at much higher density to improve sensor sensitivity and specificity. The scFv-QCM biosensors showed excellent sensitivity (detection limit, 2.2 ± 0.9 nM) and specificity with a dissociation constant K d = (1.54 ± 0.59) × 10 −7 M. CYP1B1 were quantitatively detected in normal and malignant cell lysates (e.g., human T47D breast cancer cell microsomes). Results demonstrate that an anti-CYP1B1 scFv-QCM immunosensor could be used to detect P450 enzymes in biological samples.The cytochrome P450 gene superfamily encodes multifunctional phase I enzymes that are involved in the metabolism of many drugs and dietary substances and in the synthesis of steroid hormones and other extracellular lipid signaling molecules. 1 Not surprisingly, cytochrome P450s (CYPs) have been implicated to play important roles in a wide variety of human diseases ranging from diabetes to malignancies. 2 Because of their important functions in normal physiology and disease, it would be desirable to measure CYPs. To date, CYPs have been visualized by immunocytochemistry and localized within the microsomal (endoplasmic reticulum) compartment of the cell. However, attempts to quantitate the concentration of CYPs have been unsuccessful with existing methods because of the location in the complex microsomal membrane, which consists of a mixture of proteins and lipids containing the embedded CYPs. Thus, individual CYPs have not been measured directly by existing methods but only assessed indirectly via the determination of their catalytic products.In the present study, we have developed a novel analytical approach, which was based on a piezoimmunosensor, to detect and quantitate individual CYPs in cellular extracts. As a prototype, we selected one member of the CYP family, CYP1B1, because it has been implicated in the estrogen carcinogenesis of breast cancer, in which it is overexpressed. 3,4 Several studies have also targeted CYP1B1 as a universal tumor antigen, using specific cytotoxic T cells for *To whom correspondence should be addressed. E-mail: zeng@oakland.edu., Tel: 248-370-2881. Fax: 248-370-2321 NIH Public Access The establish...

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Genetic Testing for Enzymes of Drug Metabolism: Does It Have Clinical Utility for Pain Medicine at the Present Time? A Structured Review

Abstract: It was concluded that genomic testing for enzymes of drug metabolism has significant potential for improving the efficacy of drug treatment and reducing adverse drug reactions. Recommendations for when such testing would be useful are outlined.

Cited by 32 publications

References 45 publications

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

Cytochrome P450 Enzyme Polymorphism Frequency in Indigenous and Native American Populations: A Systematic Review

Recombinant Antibody Piezoimmunosensors for the Detection of Cytochrome P450 1B1

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