scholarly journals Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel

2006 ◽  
Vol 174 (12) ◽  
pp. 1715-1722 ◽  
Author(s):  
J.-W. Suh
Keyword(s):  
Cytochrome P450 ◽  
Increased Risk ◽  
Cytochrome P450 3A5

scholarly journals Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance

2013 ◽  
Vol 6 (4) ◽  
pp. 159-184 ◽  
Author(s):  
Anthony Samsel ◽  
Stephanie Seneff
Keyword(s):  
Cytochrome P450 ◽  
Celiac Disease ◽  
Kidney Failure ◽  
Macrocytic Anemia ◽  
Gut Bacteria ◽  
Environmental Toxins ◽  
Nutritional Deficiencies ◽  
Cytochrome P450 Enzymes ◽  
Gluten Intolerance ◽  
Increased Risk

ABSTRACT Celiac disease, and, more generally, gluten intolerance, is a growing problem worldwide, but especially in North America and Europe, where an estimated 5% of the population now suffers from it. Symptoms include nausea, diarrhea, skin rashes, macrocytic anemia and depression. It is a multifactorial disease associated with numerous nutritional deficiencies as well as reproductive issues and increased risk to thyroid disease, kidney failure and cancer. Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup®, is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate’s strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate’s known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin’s lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of "ripening" sugar cane with glyphosate may explain the recent surge in kidney failure among agricultural workers in Central America. We conclude with a plea to governments to reconsider policies regarding the safety of glyphosate residues in foods

scholarly journals Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Xu Hao ◽  
Kelu Hou ◽  
Lei Hu ◽  
Jingyuan Shang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Adverse Events ◽  
Success Rate ◽  
Clinical Efficacy ◽  
Search Algorithm ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact ◽  
Cyp2c19 Polymorphisms

Aims: To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole. Methods: We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to March 18, 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity and neurotoxicity. Results: A total of 20 studies were included. Intermediate metabolizers (IMs) and Poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) (risk ratio (RR): 1.18, 95% confidence interval (CI): 1.03~1.34, I2=0%, p=0.02; RR: 1.28, 95%CI: 1.06~1.54, I2=0%, p=0.01). PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR: 2.18, 95%CI: 1.35~3.53, I2=0%, p=0.001; RR: 1.80, 95% CI: 1.23~2.64, I2=0%, p=0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR: 1.60, 95%CI: 0.94~2.74, I2=27%, p=0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity. Conclusions: IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deservers clinical attention.

The Cytochrome P450 3A5 Non-Expressor Kidney Allograft as a Risk Factor for Calcineurin Inhibitor Nephrotoxicity

2018 ◽  
Vol 47 (3) ◽  
pp. 182-190 ◽  
Author(s):  
Suwasin Udomkarnjananun ◽  
Natavudh Townamchai ◽  
Pajaree Chariyavilaskul ◽  
Kroonpong Iampenkhae ◽  
Krit Pongpirul ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Calcineurin Inhibitor ◽  
Cox Regression ◽  
Kidney Tissue ◽  
Acute Rejection Episode ◽  
Genotype 3 ◽  
Kidney Allograft ◽  
Cytochrome P450 3A5 ◽  
Calcineurin Inhibitor Nephrotoxicity ◽  
Donor Genotype

Background: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. Methods: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3). The primary outcomes were allograft complications including calcineurin inhibitor (CNI) nephrotoxicity and acute rejection episode. Results: Of the 50 enrolled patients, 21 donors were expressors and 29 donors were the non-expressors. Tacrolimus trough concentrations were similar between the 2 genotypes. The incidence of CNI nephrotoxicity was higher in recipients with non-expressor donor genotype compared with the expressor donor genotype (72.4 vs. 33.3%, p = 0.006). CNI nephrotoxicity incidence was not different when recipient’s genotypes were compared. Multivariate analysis from Cox-regression showed a hazard ratio of 3.18 (p = 0.026) for CNI nephrotoxicity in the non-expressor compared with the expressor donor. The recipient CYP3A5 genotypes did not significantly contribute to CNI nephrotoxicity. Kaplan-Meier analysis demonstrated the lowest CNI nephrotoxicity-free survival in recipients with the expressor genotype who received allograft from the non-expressor donors (p = 0.005). Conclusion: In conclusion, our results suggest that donor CYP3A5 non-expressor genotype (*3/*3) is a risk for CNI nephrotoxicity.

Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers

2008 ◽  
Vol 18 (6) ◽  
pp. 487-493 ◽  
Author(s):  
Takayuki Seo ◽  
Punam Pahwa ◽  
Helen H. McDuffie ◽  
Keigo Yurube ◽  
Masayoshi Egoshi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Lung Function ◽  
Cytochrome P450 3A5 ◽  
Grain Workers

Pharmacogenetic biomarkers: cytochrome P450 3A5

2012 ◽  
Vol 413 (17-18) ◽  
pp. 1312-1317 ◽  
Author(s):  
Iain A.M. MacPhee
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A5
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