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    Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation
    (FRONTIERS MEDIA SA, 2020) Müderrisoğlu, Ahmet; Babaoğlu, Elif; Korkmaz, Elif Tuğçe; Ongun, Mert C.; Karabulut, Erdem; İskit, Alper B.; Emri, Salih
    Objectives To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. Methods 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. Results Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). Conclusion Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.
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    Effects of PON1 QR192 genetic polymorphism and paraoxonase, arylesterase activities on deep vein thrombosis
    (Walter De Gruyter Gmbh, 2023) Akbalik, Hasim; Polat, Muhammet Fevzi; Müderrisoğlu, Ahmet; Er, Zafer Cengiz; Caniklioğlu, Ayşen; Ekim, Meral; Ekim, Hasan
    Objectives: We aimed to evaluate PON1 QR192 polymorphism's (rs662) effects on levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein, and paraoxonase-arylesterase activities among deep vein thrombosis patients and healthy subjects. Methods: Forty-five deep vein thrombosis patients and 45 healthy subjects participated in the study. Genetic analysis was performed by using polymerase chain reaction and sequencing. Paraoxonase and arylesterase enzyme activities were determined by a spectrophotometer. Serum levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein were measured by a similar method. Results: There were no statistically significant differences between patients and controls regarding the frequency of variant allele for the PON1 QR192 polymorphism, activities of paraoxonase-arylesterase, and level of high-density lipoprotein-cholesterol. Triglyceride, total cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein levels were significantly higher in patients compared to controls (p values were 0.005, 0.0002, 0.009, 0.0009, <0.0001, respectively.) Paraoxonase activity was found to be associated with PON1 QR192 genetic polymorphism (p<0.0001). However, we observed no association of PON1 QR192 polymorphism with arylesterase activity and, levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein. Conclusions: There was no statistically significant difference between deep vein thrombosis patients and healthy subjects regarding variant allele frequency for the PON1 QR192 genetic polymorphism. In addition, paraoxonase and arylesterase activities were similar among the groups. These results indicate that PON1 QR192 genetic polymorphism and activity levels of paraoxonase-arylesterase have no effect on the development of deep vein thrombosis.
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    MTHFR C677T (rs1801133) genetic polymorphism is associated with development risk of essential hypertension in the Turkish population
    (Springernature, 2022) Er, Zafer Cengiz; Müderrisoğlu, Ahmet; Ekim, Meral; Ekim, Hasan
    Background Hypertension is a serious condition that is spread worldwide and may lead to severe complications such as heart attack, stroke, hypertensive retinopathy, and renal failure. Although some genetic and environmental risk factors are known to play a role in the etiology of hypertension, like most of the other multi-factorial diseases, its etiology is yet to be fully elucidated. Our study aimed to investigate the effects of methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and A1298C (rs1801131), factor V Leiden (FVL) G1691A (rs6025), and prothrombin (PT) G20210A (rs1799963) genetic polymorphisms on the development risk of essential hypertension and level of blood pressure in hypertensive patients. Results The frequency of the homozygous polymorphic TT genotype for the MTHFR C677T polymorphism was significantly higher in male hypertensive patients than in the male control group (27% vs 6.3%, p = 0.028). The rate of the variant T allele for the MTHFR C677T polymorphism was also significantly higher in male hypertensive patients compared to male healthy controls (51.4% vs 21.9%, p = 0.0004). There was no difference among hypertensive patients and healthy controls regarding the frequencies of MTHFR A1298C, FVL G1691A and PT G20210A polymorphisms. In addition, we found no difference between genotype groups regarding systolic and diastolic blood pressure levels in hypertensive patients. Conclusions Homozygous polymorphic TT genotype and variant T allele for the MTHFR C677T polymorphism may be considered as a risk factor for the development of essential hypertension in the Turkish male population.