Significance of the genetic polymorphism of CYP2D6 and NAT2 in patients with inflammatory bowel diseases

Dudarewicz, Michał; Rychlik‐Sych, Mariola; Barańska, Małgorzata; Wojtczak, Andrzej; Trzciński, Radzisław; Dziki, Adam; Skrętkowicz, Jadwiga

doi:10.1016/j.pharep.2014.04.002

Cited by 4 publications

(5 citation statements)

References 22 publications

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“…Dudarewicz et al[59] have analysed CYP2D6 genotypes *1 (wild type), *3 and *4 using the PCR-RFLP method in 258 people from central Poland; 65 patients with UC and 50 with Crohn’s disease (CD); and 143 healthy controls. They announced that despite the fact that the odds ratio (OR) was higher in carriers of the CYP2D6*1 /CYP2D6*3 genotype [extensive metabolizer (EM)], there was no factually signiﬁcant difference in the recurrence of the CYP2D6 alleles in patients with UC and CD.…”

Section: Cyp2d6mentioning

confidence: 99%

Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis

Sen

Stark

2019

WJG

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Cytochromes P450s (CYPs) are terminal enzymes in CYP dependent monooxygenases, which constitute a superfamily of enzymes catalysing the metabolism of both endogenous and exogenous substances. One of their main tasks is to facilitate the excretion of these substances and eliminate their toxicities in most phase 1 reactions. Endogenous substrates of CYPs include steroids, bile acids, eicosanoids, cholesterol, vitamin D and neurotransmitters. About 80% of currently used drugs and environmental chemicals comprise exogenous substrates for CYPs. Genetic polymorphisms of CYPs may affect the enzyme functions and have been reported to be associated with various diseases and adverse drug reactions among different populations. In this review, we discuss the role of some critical CYP isoforms (CYP1A1, CYP2D6, CYP2J2, CYP2R1, CYP3A5, CYP3A7, CYP4F3, CYP24A1, CYP26B1 and CYP27B1) in the pathogenesis or aetiology of ulcerative colitis concerning gene polymorphisms. In addition, their significance in metabolism concerning ulcerative colitis in patients is also discussed showing a clear underestimation in genetic studies performed so far.

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Section: Cyp2d6mentioning

confidence: 99%

Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis

Sen

Stark

2019

WJG

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“…One of the enzymes involved in xenobiotic metabolism is NAT2. NAT2 is a phase II enzyme that catalyzes the acetylation reactions to perform the detoxification of xenobiotics, including environmental/dietary compounds, carcinogens, and drugs [ 50 – 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…The polymorphisms of the NAT2 gene have major pharmacogenetic considerations as they lead to adverse drug reactions and individual differences in drug response [ 51 , 52 ]. NAT2 polymorphisms have also clinical importance, due to the fact that these polymorphisms lead to susceptibility to many diseases such as autoimmune diseases and cancer, for which the etiopathogenesis is affected by environmental factors [ 40 , 47 , 50 , 56 – 64 ]. Indeed, psoriasis is one of these diseases with an etiopathogenesis affected by environmental factors.…”

Section: Discussionmentioning

confidence: 99%

“…It performs detoxification of xenobiotics, which have the structure of aromatic amines, hydrazine, sulphonamides, and aliphatic amines, by acetylation reactions. These xenobiotics include environmental and dietary compounds, carcinogens, and drugs used to treat a variety of diseases, particularly tuberculosis, AIDS-related complex diseases, psoriatic arthritis, and hypertension [ 50 – 52 ]. NAT2 enzyme is encoded by intronless NAT2 gene that is located at 8p22.…”

Section: Introductionmentioning

confidence: 99%

“…There are a number of studies showing that NAT2 gene polymorphisms lead to increased susceptibility to various diseases, primarily cancer [ 40 , 56 – 61 ] and autoimmune disorders [ 47 , 50 , 62 – 64 ]. However, to the best of our knowledge, there are only two studies on the association of NAT2 gene variants with psoriasis vulgaris [ 65 , 66 ].…”

Section: Introductionmentioning

confidence: 99%

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NAT2Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris

Dursun

Zamani

et al. 2018

BioMed Research International

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Psoriasis is a common, chronic, and autoimmune skin disease. Factors that play a role in etiopathogenesis of psoriasis include internal factors such as genetic susceptibility and immunological factors and external factors such as stress, infection, trauma, drug, and environmental compounds. N-acetyltransferase 2 (NAT2) is a xenobiotic enzyme that is involved in the metabolism of drugs, environmental toxins, and carcinogens. In this study, we aimed to demonstrate whether the variations in the NAT2 gene lead to a predisposition to psoriasis by affecting the enzyme's ability to metabolize drugs and environmental components or not. Three polymorphisms (rs1799929, rs1799930, and rs1799931) in NAT2 gene were genotyped and compared by real-time PCR method in 260 psoriasis vulgaris patients and 200 healthy controls. There was no difference in the genotype distributions and allele frequencies of polymorphisms between psoriasis vulgaris patients and controls. When the effects of polymorphisms on the clinical features of the disease, such as onset age and severity, are assessed, it has been found that rs1799930 and rs1799929 are, respectively, associated with early onset age and severity of the disease. In conclusion, rs1799929, rs1799930, and rs1799931 polymorphisms of the NAT-2 gene do not appear to be a risk factor for the development of psoriasis. Conversely, they may have an effect on either more severe or early onset cases of the disease.

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Association between Functional CYP2D6 Polymorphisms and Susceptibility to Autoimmune Diseases: A Meta-Analysis

Lee

Bae

2016

Immunological Investigations

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Significance of the genetic polymorphism of CYP2D6 and NAT2 in patients with inflammatory bowel diseases

Abstract: Polymorphism of the gene encoding CYP2D6 does not affect the incidence of inflammatory bowel diseases. The carriers of the NAT2*7 allele which determines slow acetylation may be more predisposed to inflammatory bowel diseases, including ulcerative colitis and Crohn's disease.

Cited by 4 publications

References 22 publications

Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis

Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis

NAT2Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris

Association between Functional CYP2D6 Polymorphisms and Susceptibility to Autoimmune Diseases: A Meta-Analysis

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