Cytochrome P450 (CYP450,2D6*A), N-acetyltransferase-2 (NAT2*7, A) and multidrug resistance 1 (MDR1 3435 T) alleles collectively increase risk of ulcerative colitis

Farzaneh Lotfi, Fariborz Bahrehmand, Asad Vaisi-Raygani, Reza Khodarahmi, Maryam Tanhapour, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed

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Abstract

Background: Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (UC) may not only be an auxiliary agent in diagnosis but also could be an effective pharmacotherapy for inflammatory bowel disease (IBD). The aim of the present case-control study was to determine the association of cytochrome P450 2D6 (CYP2D6 *4), N-acteyltransferase-2 (NAT2*7) and multidrug resistance 1 (MDR1) 3435 C/T genotypes with UC susceptibility and thiopurine methyltransferase (TPMT) enzyme activity. Methods: TPMT activity was measured by high performance liquid chromatography (HPLC) and genotypes for the 3 mentioned polymorphisms were determined in 215 unrelated UC patients and 212 unrelated healthy controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in a Kurdish population from Iran. Results: CYP2D6*4 A allele, NAT2*7 A and MDR1 3435 C/T alleles act synergistically to increase the risk of UC by 3.49 times. The frequency of the A allele of CYP2D6*4 was significantly higher in UC patients (12.6%) compared to control subjects (8.5%, P = 0.046) that significantly increased the risk of UC by 1.56-fold (P = 0.047). The frequencies of NAT2*7 genotypes and alleles were similar in both studied groups. Conclusion: The most important outcome of this study is that for the first time we demonstrated the simultaneous presence of TMDR1, A CYP2D6*4 and A NAT2*7 alleles robustly increased the risk of developing UC by 3.49-fold. The current study suggests that CYP2D6*4 and MDR1 3435 C/T gene polymorphisms may be risk factors for UC susceptibility.

Original languageEnglish (US)
Pages (from-to)530-535
Number of pages6
JournalArchives of Iranian medicine
Volume21
Issue number11
StatePublished - Nov 1 2018

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Cytochrome P-450 CYP2D6
Acetyltransferases
Multiple Drug Resistance
Ulcerative Colitis
Alleles
thiopurine methyltransferase
Genotype
Enzymes
Iran
Inflammatory Bowel Diseases
Gene Frequency
Restriction Fragment Length Polymorphisms
Case-Control Studies
High Pressure Liquid Chromatography
Outcome Assessment (Health Care)
Drug Therapy
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Cytochrome P450 (CYP450,2D6*A), N-acetyltransferase-2 (NAT2*7, A) and multidrug resistance 1 (MDR1 3435 T) alleles collectively increase risk of ulcerative colitis. / Lotfi, Farzaneh; Bahrehmand, Fariborz; Vaisi-Raygani, Asad; Khodarahmi, Reza; Tanhapour, Maryam; Kiani, Amir; Rahimi, Zohreh; Pourmotabbed, Tayebeh.

In: Archives of Iranian medicine, Vol. 21, No. 11, 01.11.2018, p. 530-535.

Research output: Contribution to journalArticle

Lotfi, Farzaneh ; Bahrehmand, Fariborz ; Vaisi-Raygani, Asad ; Khodarahmi, Reza ; Tanhapour, Maryam ; Kiani, Amir ; Rahimi, Zohreh ; Pourmotabbed, Tayebeh. / Cytochrome P450 (CYP450,2D6*A), N-acetyltransferase-2 (NAT2*7, A) and multidrug resistance 1 (MDR1 3435 T) alleles collectively increase risk of ulcerative colitis. In: Archives of Iranian medicine. 2018 ; Vol. 21, No. 11. pp. 530-535.
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abstract = "Background: Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (UC) may not only be an auxiliary agent in diagnosis but also could be an effective pharmacotherapy for inflammatory bowel disease (IBD). The aim of the present case-control study was to determine the association of cytochrome P450 2D6 (CYP2D6 *4), N-acteyltransferase-2 (NAT2*7) and multidrug resistance 1 (MDR1) 3435 C/T genotypes with UC susceptibility and thiopurine methyltransferase (TPMT) enzyme activity. Methods: TPMT activity was measured by high performance liquid chromatography (HPLC) and genotypes for the 3 mentioned polymorphisms were determined in 215 unrelated UC patients and 212 unrelated healthy controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in a Kurdish population from Iran. Results: CYP2D6*4 A allele, NAT2*7 A and MDR1 3435 C/T alleles act synergistically to increase the risk of UC by 3.49 times. The frequency of the A allele of CYP2D6*4 was significantly higher in UC patients (12.6{\%}) compared to control subjects (8.5{\%}, P = 0.046) that significantly increased the risk of UC by 1.56-fold (P = 0.047). The frequencies of NAT2*7 genotypes and alleles were similar in both studied groups. Conclusion: The most important outcome of this study is that for the first time we demonstrated the simultaneous presence of TMDR1, A CYP2D6*4 and A NAT2*7 alleles robustly increased the risk of developing UC by 3.49-fold. The current study suggests that CYP2D6*4 and MDR1 3435 C/T gene polymorphisms may be risk factors for UC susceptibility.",
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T1 - Cytochrome P450 (CYP450,2D6*A), N-acetyltransferase-2 (NAT2*7, A) and multidrug resistance 1 (MDR1 3435 T) alleles collectively increase risk of ulcerative colitis

AU - Lotfi, Farzaneh

AU - Bahrehmand, Fariborz

AU - Vaisi-Raygani, Asad

AU - Khodarahmi, Reza

AU - Tanhapour, Maryam

AU - Kiani, Amir

AU - Rahimi, Zohreh

AU - Pourmotabbed, Tayebeh

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (UC) may not only be an auxiliary agent in diagnosis but also could be an effective pharmacotherapy for inflammatory bowel disease (IBD). The aim of the present case-control study was to determine the association of cytochrome P450 2D6 (CYP2D6 *4), N-acteyltransferase-2 (NAT2*7) and multidrug resistance 1 (MDR1) 3435 C/T genotypes with UC susceptibility and thiopurine methyltransferase (TPMT) enzyme activity. Methods: TPMT activity was measured by high performance liquid chromatography (HPLC) and genotypes for the 3 mentioned polymorphisms were determined in 215 unrelated UC patients and 212 unrelated healthy controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in a Kurdish population from Iran. Results: CYP2D6*4 A allele, NAT2*7 A and MDR1 3435 C/T alleles act synergistically to increase the risk of UC by 3.49 times. The frequency of the A allele of CYP2D6*4 was significantly higher in UC patients (12.6%) compared to control subjects (8.5%, P = 0.046) that significantly increased the risk of UC by 1.56-fold (P = 0.047). The frequencies of NAT2*7 genotypes and alleles were similar in both studied groups. Conclusion: The most important outcome of this study is that for the first time we demonstrated the simultaneous presence of TMDR1, A CYP2D6*4 and A NAT2*7 alleles robustly increased the risk of developing UC by 3.49-fold. The current study suggests that CYP2D6*4 and MDR1 3435 C/T gene polymorphisms may be risk factors for UC susceptibility.

AB - Background: Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (UC) may not only be an auxiliary agent in diagnosis but also could be an effective pharmacotherapy for inflammatory bowel disease (IBD). The aim of the present case-control study was to determine the association of cytochrome P450 2D6 (CYP2D6 *4), N-acteyltransferase-2 (NAT2*7) and multidrug resistance 1 (MDR1) 3435 C/T genotypes with UC susceptibility and thiopurine methyltransferase (TPMT) enzyme activity. Methods: TPMT activity was measured by high performance liquid chromatography (HPLC) and genotypes for the 3 mentioned polymorphisms were determined in 215 unrelated UC patients and 212 unrelated healthy controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in a Kurdish population from Iran. Results: CYP2D6*4 A allele, NAT2*7 A and MDR1 3435 C/T alleles act synergistically to increase the risk of UC by 3.49 times. The frequency of the A allele of CYP2D6*4 was significantly higher in UC patients (12.6%) compared to control subjects (8.5%, P = 0.046) that significantly increased the risk of UC by 1.56-fold (P = 0.047). The frequencies of NAT2*7 genotypes and alleles were similar in both studied groups. Conclusion: The most important outcome of this study is that for the first time we demonstrated the simultaneous presence of TMDR1, A CYP2D6*4 and A NAT2*7 alleles robustly increased the risk of developing UC by 3.49-fold. The current study suggests that CYP2D6*4 and MDR1 3435 C/T gene polymorphisms may be risk factors for UC susceptibility.

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