Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study

Habibi, Mohsen; Mirfakhraie, Reza; Khani, Maryam Allahverdi; Rakhshan, Azadeh; Azargashb, Eznollah; Pouresmaeili, Farkhondeh

doi:10.1016/j.gene.2017.08.038

Cited by 9 publications

(9 citation statements)

References 58 publications

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“…Another recent study showed an association of the UGT2B17 deletion with higher risk of benign prostatic hyperplasia (BPH) and a greater risk for the combination of the UGT2B17 deletion and the UGT2B15 D85 variant, although this study did not find any associations with frank prostate cancer (243).…”

Section: Prostate Cancercontrasting

confidence: 89%

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms

Meech

McKinnon

et al. 2019

Physiological Reviews

253

168

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UDP-glycosyltransferases (UGTs) catalyze the covalent addition of sugars to a broad range of lipophilic molecules. This biotransformation plays a critical role in elimination of a broad range of exogenous chemicals and by-products of endogenous metabolism, and also controls the levels and distribution of many endogenous signaling molecules. In mammals, the superfamily comprises four families: UGT1, UGT2, UGT3, and UGT8. UGT1 and UGT2 enzymes have important roles in pharmacology and toxicology including contributing to interindividual differences in drug disposition as well as to cancer risk. These UGTs are highly expressed in organs of detoxification (e.g., liver, kidney, intestine) and can be induced by pathways that sense demand for detoxification and for modulation of endobiotic signaling molecules. The functions of the UGT3 and UGT8 family enzymes have only been characterized relatively recently; these enzymes show different UDP-sugar preferences to that of UGT1 and UGT2 enzymes, and to date, their contributions to drug metabolism appear to be relatively minor. This review summarizes and provides critical analysis of the current state of research into all four families of UGT enzymes. Key areas discussed include the roles of UGTs in drug metabolism, cancer risk, and regulation of signaling, as well as the transcriptional and posttranscriptional control of UGT expression and function. The latter part of this review provides an in-depth analysis of the known and predicted functions of UGT3 and UGT8 enzymes, focused on their likely roles in modulation of levels of endogenous signaling pathways.

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Section: Prostate Cancercontrasting

confidence: 89%

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms

Meech

McKinnon

et al. 2019

Physiological Reviews

253

168

View full text Add to dashboard Cite

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“…Blood samples were taken from the control subjects in the same way and then DNA extraction was performed (DiatomTM DNA prep kit and in some samples using salting out method). The PCR conditions were based on previously works [33,34]. The forward and reverse primers for examining the studied copy number variations and the gene polymorphisms are shown in Table 1.…”

Section: Informed Consent Was Received From Each Patient Dna Extracti...mentioning

confidence: 99%

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2022

Journal of Bioinformatics and Comparative Genomics

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After lung cancer, prostate cancer has the highest mortality rate. Early and accurate diagnosis of this heterogeneous cancer promises more effective treatment. At present biopsy is the only definitive method of diagnosing the disease. Many gene loci are associated with increased susceptibility to this cancer. Here, the relationship between tumor necrosis factor alpha (TNF-α) gene variants and glucuronidation pathway gene variants with increased risk of prostate cancer in a population of Iranian men has been investigated. Materials and methods:Blood samples were collected from 360 men including 120 healthy, 120 with benign prostate hyperplasia (BPH), and 120 patients with prostate cancer (PCa). DNA was extracted and tested for each variant with specific primers and PCR based methods. Data were analyzed using agarose and polyacrylamide gel electrophoresis, SPSS software, SNP Stats and Student's t-test.Results: UGT2B17 and UGT2B15 polymorphisms were associated with BPH in comparison to the control group (P value = <0.0001 and P value = 0.007). The only significant association in the cancer group was between G Score and UGT2B15, so that 90% of patients with PCa and G score less than or equal to 6, had GG genotype (0.01). Other variants had no significant relationship with the cause of the disease. Ins Del G haplotype was more common in BPH compared to the control group (P value = 0.011).

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“…Pharmacogenetic variability may play a role for the vulnerability of ALF, but pharmacogenetic screening was not performed in any of the previously published cases. Paracetamol is subjected to metabolism via several phase I and phase II enzymes exhibiting genetic polymorphism, including CYP1A2, CYP2D6 and UGT2B15 . We present a patient with NMD who developed fatal ALF following the administration of therapeutic doses of paracetamol.…”

Section: Introductionmentioning

confidence: 99%

“…Paracetamol is subjected to metabolism via several phase I and phase II enzymes exhibiting genetic polymorphism, including CYP1A2, CYP2D6 and UGT2B15. [13][14][15] We present a patient with NMD who developed fatal ALF following the administration of therapeutic doses of paracetamol. In this case, pharmacogenetic analyses of drug-metabolizing enzymes were conducted in order to search for possible explanations for this unexpected fatal outcome.…”

Section: Introductionmentioning

confidence: 99%

Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug‐metabolizing enzymes

Lao

Molden

Kringen

et al. 2020

Basic Clin Pharma Tox

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Paracetamol has a good safety profile, but pharmacogenetic differences in drug‐metabolizing enzymes may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where pharmacogenetic screening was conducted. This 30‐year‐old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the formation of toxic intermediate metabolite, N‐acetyl‐p‐benzo‐quinone imine (NAPQI). He also had decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI may add to the risk of toxicity. This case may indicate that pharmacogenetic variability is of potential relevance for the risk of paracetamol‐induced hepatotoxicity in patients with neuromuscular diseases. Further studies should investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of hepatotoxicity in these patients at therapeutic doses of paracetamol and hence provide information for selection of analgesic treatment.

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Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study

Cited by 9 publications

References 58 publications

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms

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Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug‐metabolizing enzymes

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