scholarly journals The Implication of the Polymorphisms of COX-1, UGT1A6, and CYP2C9 among Cardiovascular Disease (CVD) Patients Treated with Aspirin

2015 ◽  
Vol 18 (3) ◽  
pp. 474 ◽  
Author(s):  
Nur Jalinna Abdul Jalil ◽  
Zakaria Bannur ◽  
A. Derahman ◽  
O. Maskon ◽  
Noor Darinah ◽  
...  

PURPOSE:  Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated. METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR). RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 – 33.19; P = 0.033). CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.


2018 ◽  
Vol 6 (4) ◽  
pp. 98 ◽  
Author(s):  
Fatemeh Karami ◽  
Maliheh Askari ◽  
Mohammad Modarressi

Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most important variants including rs5918 T > C and rs1800790 G > A were selected to be studied in women affected by RPL. Three milliliters of peripheral blood were drawn from 110 women with history of at least two consecutive spontaneous abortion and 110 healthy women controls. rs5918 T > C and rs1800790 G > A of HPA-1 and FGB genes, respectively, were selected to be analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR_RFLP) following DNA isolation using QIAamp DNA Blood Mini Kit. Heterozygote genotype (TC) of HPA-1 gene rs5918 polymorphism was significantly associated with risk of RPL (p-value = 0.02). Although, rs1800790 G > A of FGB gene was not associated with RPL, its combination with rs5918 polymorphism was associated with increased risk of RPL. Owing to the critical roles of FGB and HPA-1 genes in coagulation, and thrombosis and several confinements on the meaningful association between the combination of those polymorphism with risk of RPL, including them in the thrombophilia panel may increase detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are required to shed light on the exact role of the studied gene polymorphism, especially rs1800790 G > A of FGB gene variant in pathogenesis of RPL.



1998 ◽  
Vol 114 ◽  
pp. A82
Author(s):  
T. Brzozowski ◽  
P.C. Konturek ◽  
R. Pajdo ◽  
N. Nagraba ◽  
A. Szczeklik ◽  
...  


2021 ◽  
Vol 6 (1) ◽  
pp. 31-35
Author(s):  
Charliandri Saputra Wahab ◽  
J. Nugroho Eko Putranto ◽  
Ike Dhiah Rochmawati

Polimorfisme genetik COX-1 (Cyclooxygenase 1) menjadi salah satu faktor penyebab variasi respon terhadap agregasi platelet. Variasi tersebut dapat menimbulkan Coronary Arthery Disease (CAD) pada pasien penyakit jantung koroner (PJK). Penelitian ini dilakukan di RSUD Sidoarjo di Jawa Timur selama 1 bulan yaitu terhitung mulai bulan November hingga Desember 2017 dengan melibatkan 30 pasien. Metode penelitian yang digunakan yaitu Polymerase Chain Reaction (PCR) agar pemeriksaan polimorfisme COX-1 dan metode Light Transmittance  Aggregometry (LTA) untuk pengukuran agregasi platelet. Dari 30 pasien yang terlibat dengan penelitian ini didapatkan jenis polimorfisme COX-1 homozygout (wild type) sebanyak 4 pasien dengan nilai bp pada kisaran rentang 233-243dan Heterozygot sebanyak 26 pasien dengan kisaran rentang 244-294. Analisis yang dilakukan agar mengetahui hubungan antara polimorfisme COX-1 terhadap agregasi platelet pada pasien PJK yaitu analisis inferensial, dimana diperoleh nilai p=0,423. Dari hasil uji analisis yang diperoleh, maka dapat diambil kesimpulan bahwa tidak hubungan antara polimorfisme COX-1 terhadap agrgasi platelet.



2016 ◽  
pp. 32-36
Author(s):  
Z. V. Shuliak ◽  
E. I. Mikhailova

To study the role of IL28B gene polymorphisms in the development of chronic hepatitis C, we have determined polymorphic types of the gene at sites rs12979860 and rs8099917 using allele-specific polymerase chain reaction with real-time product detection in 21 patients with this disease. We have found the association of chronic hepatitis C with the presence of unfavorable TT genotype of gene IL28B polymorphism rs12979860, which can be regarded as a predictor of the development of this pathology. Favorable genotypes of CC rs12979860 and TT polymorphism of rs8099917 of gene IL28B are more common in healthy individuals and they are associated with higher activity of the inflammatory process in patients with chronic hepatitis C. Therefore, gene IL28B polymorphisms can affect not only the outcome of an acute viral infection but also the further course of chronic hepatitis C.



Author(s):  
Yu.V. Zhorina ◽  
S.O. Abramovskikh ◽  
G.L. Ignatova ◽  
O.G. Ploshchanskay

Bronchial asthma is a multifactorial disease underpinned by chronic inflammation. The atopic phenotype of BA implies the presence of similar molecular mechanisms of pathogenesis between the patients. The aim of this study was to analyze the associations between the development of atopic BA/its remission and the following polymorphisms of interleukin genes: IL4 (rs2243250; C-589T), IL10 (rs1800896; G-1082A; rs1800872; C-592A), and IL13 (rs20541; Arg130Gln). Using allele-specific polymerase chain reaction (PCR), we studied the listed SNPs in the mixed urban sample of patients with BA (n = 53) and the controls (n = 30) residing in South Ural. The analysis revealed that genotype АА of IL10 (rs1800872) occurred more frequently in the control group (23.3%) than in the patients with atopic BA (5.7%) (OR = 0.197; 95% CI [0.047–0.832]; р = 0.031). No differences in genotype frequencies were observed between the patients with atopic BA and the controls for other studied polymorphisms. Our study failed to demonstrate the association of the listed polymorphisms and BA remission.



2018 ◽  
Vol 60 (No. 8) ◽  
pp. 342-350 ◽  
Author(s):  
M. Zendehdel ◽  
A. Baghbanzadeh ◽  
B. Yeganeh ◽  
S. Hassanpour

Previous studies showed that cyclooxygenase 1 (COX) enzyme has an important role in lipopolysaccharide (LPS)-induced hypophagia in mammals but the effect of COX on LPS-induced hypophagia has not been studied in avian species. The current study was designed to investigate the effects of Indomethacin, a non-selective cyclooxygenase inhibitor, Aspirin (irreversible cyclooxygenase inhibitor), Piroxicam (a selective COX-1 inhibitor), and Celecoxib (a selective COX-2 inhibitor) on LPS-induced hypophagia in 3-h food-deprived (FD<sub>3</sub>) cockerels. One hundred and sixty ROSS 308 chickens were randomly divided into 5 experiments and 4 treatment groups (8 replicates in each group of experiments). Guide cannula was surgically implanted into the lateral ventricle of chickens. In Experiment 1, birds received LPS (5, 10, and 20 ng) intracerebroventricularly (ICV). In Experiment 2, chickens were intraperitoneally (i.p.) injected with Indomethacin (5&nbsp;mg/kg) prior to LPS injection (20 ng; ICV). In Experiment 3, birds were i.p. injected with Aspirin (50 mg/kg) followed by LPS injection (20 ng; ICV). In Experiment 4, chickens were given LPS (20 ng; ICV) after Piroxicam injection (10 mg/kg; i.p.). In Experiment 5, chickens were injected with Celecoxib (10 mg/kg; i.p.) prior to LPS injection (20 ng; ICV). Cumulative feed intake was determined until 8 h post-injection. According to the results, LPS significantly decreased feed intake at 4 and 8 h post injection in birds (P &le; 0.05). Furthermore, LPS-induced hypophagia was attenuated by pre-injection with Indomethacin, Aspirin, and Celecoxib (P&nbsp;&le; 0.05). However, Piroxicam had no effect on LPS-induced hypophagia (P &ge; 0.05). These results suggest that presumably COX-2 mediates LPS-induced hypophagia in broilers.



2020 ◽  
Vol 5 (3) ◽  
pp. 59-65
Author(s):  
A. N. Volkov

Aim. To explore allele and genotype frequencies of the rs8175347 polymorphism within the UGT1A1 gene in Kemerovo Region. Materials and Methods. The study sample included 64 male and 68 female inhabitants of the Kemerovo Region. Upon DNA isolation from the peripheral blood leukocytes, we conducted allele-specific polymerase chain reaction followed by electrophoretic detection of the genotype. Results. The frequency of minor allele *28 of rs8175347 polymorphism, which is associated with the downregulation of UDP-glucuronosyltransferase А1 in the liver, was 33.3%, while the frequency of *28/*28 genotype was 13.6% and did not significantly differ in the examined men and women. Conclusion. High frequency of the *28/*28 genotype in the studied sample suggests a high prevalence of reduced UDP-glucuronosyltransferase А1 activity and associated conditions including Gilbert’s syndrome and adverse drug reactions.



Author(s):  
Viren Ramadhan ◽  
Faisal Rahman ◽  
Ahmad Hamim Sadewa ◽  
Zullies Ikawati

Background: Dopamine plays an important role in mediating the rewarding properties in the abuse of drugs. The Taq1A polymorphism is a commonly studied DRD2 gene variant whereby carriers of the low-function T allele (T/T or T/C genotypes) show reduced brain dopamine function. Therefore, individuals who have the DRD2 Taq1A polymorphism will experience higher levels of drug addiction because the T allele is associated with a reduced number of dopamine binding sites in the brain. A study of this gene has been conducted in some areas but there is no research for the population of Indonesia. Objective: This study will focus on the frequency of DRD2 Taq1A gene polymorphism in the population of Indonesia and define its association with drug addiction. Method: This is an a-cross sectional study in which 182 subjects are divided into 91 drug-addicted patients and 91 nondrug-addicted control subjects. The genotype analysis was carried out by a modified allele-specific Polymerase Chain Reaction (PCR) method. Results: The frequency of the T/T and C/T was significantly higher in the addicted than control subjects. They are 6.6% and 63.7% compared to 0% and 3.3%. Likewise, the T allele is more frequent in the addicted equal to 38% compared to only 2% in the control subjects. The frequency of the T allele between the addicted and control subjects shows a significantly different (p-value < 0.0001; 95% CI), with the addicted being at a higher risk of having the T allele (OR = 37.3; 95% CI [11.46-121.29]). Results: The frequency of the T/T and C/T was significantly higher in the addicted than control subjects. They are 6.6% and 63.7% compared to 0% and 3.3%. Likewise, the T allele is more frequent in the addicted equal to 38% compared to only 2% in the control subjects. The frequency of the T allele between the addicted and control subjects shows a significantly different (p-value < 0.0001; 95% CI), with the addicted being at a higher risk of having the T allele (OR = 37.3; 95% CI [11.46-121.29]). Conclusion: A high frequency of the DRD2 Taq1A gene polymorphism between addicted patients and control subject groups. Thus, there is an association between the DRD2 Taq1A gene polymorphism and the development of drug addiction with T allele increases the predisposition to addiction.



2003 ◽  
Vol 99 (5) ◽  
pp. 1175-1179 ◽  
Author(s):  
Xiaoying Zhu ◽  
James C. Eisenach

Background The mechanisms underlying neuropathic pain are incompletely understood and its treatment is often unsatisfactory. Spinal cyclooxygenase-2 (COX-2) expression is upregulated after peripheral inflammation, associated with spinal prostaglandin production leading to central sensitization, but the role of COX isoenzymes in sensitization after nerve injury is less well characterized. The current study was undertaken to determine whether COX-1 was altered in this model. Methods Male rats underwent partial sciatic nerve transsection (PSNT) or L5-L6 spinal nerve ligation (SNL). Four weeks after PSNT and 4 h, 4 days, or 2 weeks after SNL, COX-1 immunohistochemistry was performed on the L2-S2 spinal cord. Results COX-1 immunoreactivity (COX-1-IR) was unaffected 4 h after SNL. In contrast, 4 days after SNL, the number of COX-1-IR cells increased in the ipsilateral spinal cord. COX-1-IR increased in cells with glial morphology in the superficial laminae, but decreased in the rest of the ipsilateral spinal cord 4 weeks after PSNT and 2 weeks after SNL. These changes in immunostaining were greatest at the L5 level. Conclusion These data suggest that COX-1 expression in the spinal cord is not static, but changes in a time- and laminar-dependent manner after nerve injury. These anatomic data are consistent with observations by others that spinally administered specific COX-1 inhibitors may be useful to prevent and treat neuropathic pain.



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