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NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

ABSTRACT: 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.

SUBMITTER: Dursun R

PROVIDER: S-EPMC6016222 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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<i>NAT2</i> Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

Dursun Recep R Dursun Hatice Gül HG Zamani Ayşe Gül AG Yıldırım Mahmut Selman MS Çınar İlknur İ

BioMed research international 20180611

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 <i> ...[more]

PMID: 29992137

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Project description:BackgroundN-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus resulting in rapid or slow acetylator phenotypes. The acetylator status may, therefore, predispose drug-induced toxicities and cancer risks, such as bladder, colon and lung cancer. Indeed, some studies demonstrate a positive association between NAT2 rapid acetylator phenotype and colon cancer, but results are inconsistent. The role of NAT2 acetylation status in lung cancer is likewise unclear, in which both the rapid and slow acetylator genotypes have been associated with disease.MethodsWe investigated three genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), of the NAT2 gene, which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects, 92 colon and 67 lung cancer patients for these genetic variations. As there is a recent meta-analysis of NAT2 studies on colon cancer (unlike in lung cancer), we have also undertaken a systematic review of NAT2 studies on lung cancer, and we incorporated our results in a meta-analysis consisting of 16 studies, 3,865 lung cancer patients and 6,077 control subjects.ResultsWe did not obtain statistically significant differences in NAT2 allele and genotype frequencies in colon cancer patients and control group. Certain genotypes, however, such as [c.590AA+c.857GA] and [c.590GA+c.857GA] were absent among the colon cancer patients. Similarly, allele frequencies in lung cancer patients and controls did not differ significantly. Nevertheless, there was a significant increase of genotypes [c.590GA] and [c.481CT+c.590GA], but absence of homozygous c.590AA and [c.590AA+c.857GA] in the lung cancer group. Meta-analysis of 16 NAT2 studies on lung cancer did not evidence an overall association of the rapid or slow acetylator status to lung cancer. Similarly, the summary odds ratios obtained with stratified meta-analysis based on ethnicity, and smoking status were not significant.ConclusionOur study failed to show an overall association of NAT2 genotypes to either colon or lung cancer risk.

Dataset Information

NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

Publications

<i>NAT2</i> Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

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