Shek Aleksandr B, Kurbanov Ravshanbek D, Alieva Rano B, Abdullaeva Guzal J, Nagay Aleksandr V, Abdullaev Alisher A, Hoshimov Shavkat U, Nizamov Ulugbek I
Republican Specialized Center of Cardiology, Tashkent, Uzbekistan.
Institute of Genetics and Plant Experimental Biology, Uzbekistan Academy of Sciences, Tashkent, Uzbekistan.
Arch Med Sci Atheroscler Dis. 2018 Jun 28;3:e83-e89. doi: 10.5114/amsad.2018.76826. eCollection 2018.
The aim was to study the pharmacogenetic determinants of switching simvastatin-intolerant ethnic Uzbek patients with coronary artery disease (CAD) to rosuvastatin treatment.
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.
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; = 0.014).
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.
本研究旨在探讨将不耐受辛伐他汀的乌兹别克族冠心病（CAD）患者换用瑞舒伐他汀治疗的药物遗传学决定因素。
本研究纳入了50例CAD患者，这些患者在服用剂量为10 - 20mg/天的辛伐他汀治疗时出现了他汀类药物诱导的不良肝脏症状，伴有转氨酶水平升高（37例升高3倍或更多）或他汀类药物诱导的不良肌肉症状，伴有血清肌酸激酶（CK）升高超过正常上限（ULN）3倍以上。对照组由50例无副作用的患者组成。采用PCR-RFLP方法对患者进行细胞色素P450（CYP）代谢酶CYP3A5（6986A>G）、CYP2C9（430C>T）、CYP2C9（1075A>C）以及肝脏摄取和外排转运体SLCO1B1（521T>C）和BCRP（ABCG2，421C>A）编码基因的多态性基因分型。
病例组的50例患者换用瑞舒伐他汀起始剂量5mg时，29例（58%）未出现不耐受症状，21例出现不良症状。在这项病例对照研究中，两组仅在CYP3A5 *3/*3基因型的患病率上存在显著差异（OR = 5.25；95%CI：1.6 - 17.8；P = 0.014）。
在相当一部分有CAD且不耐受辛伐他汀症状的乌兹别克族患者中，换用瑞舒伐他汀起始剂量时未观察到严重副作用，并且应注意在大多数情况下（72.4%），这种现象在CYP3A5（6986A>G）基因*3/*3基因型携带者中出现。
