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. 2017 Oct 5:2:e68-e75.
doi: 10.5114/amsad.2017.70597. eCollection 2017.

Simvastatin intolerance genetic determinants: some features in ethnic Uzbek patients with coronary artery disease

Aleksandr B Shek  1 , Ravshanbek D Kurbanov  1 , Guzal J Abdullaeva  1 , Aleksandr V Nagay  1 , Shavkat U Hoshimov  1 , Ulugbek I Nizamov  1 , Adolat V Ziyaeva  1 , Rano B Alieva  1
Affiliations

Simvastatin intolerance genetic determinants: some features in ethnic Uzbek patients with coronary artery disease

Aleksandr B Shek et al. Arch Med Sci Atheroscler Dis. .

Abstract

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.

Keywords: ethnic features; genetic determinants; statin intolerance.

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Conflict of interest statement

The authors declare no conflict of interest.

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