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INTRODUCTION: The aim was to study the pharmacogenetic determinants of switching simvastatin-intolerant ethnic Uzbek patients with coronary artery disease (CAD) to rosuvastatin treatment. MATERIAL AND METHODS: The study included 50 patients with CAD, who demonstrated statin-induced adverse liver symptoms, accompanied by an elevation in transaminase level (3-fold or more in 37 cases) or statin-induced adverse muscle symptoms, accompanied by elevations in serum (CK > 3 times above the upper limit of normal (ULN)) in simvastatin treatment with a dose of 10-20 mg/day. The control group consisted of 50 patients without side effects. Patients were genotyped for polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes CYP3A5(6986A>G), CYP2C9(430C>T), CYP2C9(1075A>C), and hepatic influx and efflux transporters SLCO1B1(521T>C) and BCRP(ABCG2, 421C>A) by means of the PCR-RFLP method. RESULTS: When the 50 patients of the case group were switched to the starting rosuvastatin dose of 5 mg, intolerance symptoms were not observed in 29 (58%) versus 21 with adverse symptoms. In this case-control study, the groups differed significantly only in the prevalence of the *3/*3 genotype CYP3A5 (OR = 5.25; 95% CI: 1.6-17.8; p = 0.014). CONCLUSIONS: In a considerable proportion of ethnic Uzbek patients with CAD and simvastatin intolerance symptoms, serious side effects when switching to a starting dose of rosuvastatin were not observed, and it should be noted that in most cases (72.4%) this phenomenon was observed among the carriers of *3/*3 genotype of the CYP3A5 (6986A> G) gene.
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INTRODUCTION: The objective is to study the influence of CYP3A5 (6986A>G), CYP2C9 (430C>T), CYP2C9 (1075A>C), SLCO1B1 (521T>C) and BCRP (ABCG2, 421C>A) gene polymorphisms on the development of simvastatin intolerance in ethnic Uzbek patients with coronary artery disease (CAD). MATERIAL AND METHODS: The case group contained 50 patients with clinical simvastatin-induced intolerance symptoms; the control group contained 50 patients without side-effects. Genotyping was performed by means of the PCR-RFLP method. RESULTS: Among 37 patients with simvastatin-induced liver symptoms the *3/*3 genotype of the CYP3A5 gene (p = 0.0001) and variant genotype of the CA BCRP gene were observed more frequently than in the control group (p = 0.0001). However, when the 13 patients who had statin-associated muscle symptoms (SAMS) were compared with the control group (n = 50), it was found that in the case group the 3*/3* genotype of the CYP3A5 gene (OR = 8.6; 95% CI: 2.1-34.1; p = 0.003) and C allele carriers of the gene polymorphism SLCO1B1 (OR = 3.54; 95% CI: 1.35-9.27; Χ2 = 5.7; p = 0.017) were predominant. CONCLUSIONS: The *3/*3 genotype of the CYP3A5 (6986A>G) gene and CA genotype of the BCRP (ABCG2, 421C>A) gene were associated with simvastatin-induced liver symptoms in ethnic Uzbek CAD patients, whereas in patients with simvastatin-associated muscle symptoms (SAMS), the combination of *3/*3 genotype of CYP3A5 (6986A> G) and carriage of the C allele of the SLCO1B1 gene polymorphism was predominant.
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OBJECTIVES: We investigated the association between the C825T polymorphism of the G-protein ß3 subunit (GNB3) gene with essential hypertension (EH) and cardiovascular remodeling markers in Uzbek males. STUDY DESIGN: The study included 174 Uzbek men (mean age 49±10 years) with untreated EH of stage 1-2 and 60 normotensive males. The C825T polymorphism of the GNB3 gene in the patient and control groups was determined by polymerase chain reaction. The patients were assessed with blood pressure measurements, ambulatory blood pressure monitoring, body mass index (BMI), carotid artery intima-media thickness (IMT), flow-mediated dilation (FMD) of the brachial artery, echocardiography, and urinary albumin excretion (UAE) level. RESULTS: The frequencies of the CC, CT, and TT genotypes were 36.8%, 53.5%, and 9.8% in hypertensive men, and 0%, 83.3%, and 16.7% in healthy men, respectively (p=0.0001). The frequencies of the C and T alleles were 63.8% and 36.2% in the hypertensive group, and 41.7% and 58.3% in the control group, respectively (p=0.0001). The CC genotype exhibited a significantly greater risk for hypertension compared to CT and TT genotypes (OR=72.38, 95% CI 4.40-1190.34). The C825 allele showed a higher association with hypertension in comparison to the 825T allele (OR 2.41, 95% CI 1.58-3.68). Compared to patients with the CT+TT genotypes, the CC genotype carriers had significantly higher BMI (p=0.0001), systolic (p=0.0001) and diastolic (p=0.003) blood pressures (SBP/DBP), higher nighttime DBP (p=0.042), a greater nighttime variability in both SBP and DBP (p=0.002), and greater carotid artery IMT (p=0.0001) and UAE (p=0.015) values. CONCLUSION: Our findings show a significant association between the GNB3/C825T gene polymorphism and EH, with the CC genotype exhibiting higher blood pressure, BMI, and vascular remodeling markers in Uzbek hypertensive men.
