The frequency of SLCO1B1*5 polymorphism genotypes among Russian and Sakha (Yakutia) patients with hypercholesterolemia

Abstract

IntroductionStatins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time, up to 25% of patients cannot tolerate or have to discontinue the statin therapy due to statin-induced myopathy. In a majority of cases, statin-induced myopathy is attributed to SLCO1B1 gene polymorphism. The strongest association between statin-induced myopathy and SLCO1B1 gene polymorphism was described for simvastatin. Our research was focused on the frequency of SLCO1B1*5 genetic variant in the Russian population and in the native population of Sakha (Yakutia).Materials and methodsA total of 1,071 hyperlipidemic Russian and 76 hyperlipidemic Sakha (Yakutian) patients were included in the study. Genotypes of SLCO1B1*5 (c.521T>C, rs4149056) were determined with polymerase chain reaction amplification. The results of our study were compared with data about hyperlipidemic patients in available publications.ResultsIn the Russian population 665 (62%) patients had TT genotype of SLCO1B1*5, 346 (32%) patients had TC genotype, and in 60 patients (6%) CC variant was found (Hardy–Weinberg’s chi-square test was 3.1 P=0.21). In comparison with Brazil, France, the People’s Republic of China, Japan, and the native population of Sakha (Yakutia), C-allele, which causes an increased risk of statin-induced myopathy, was found significantly more often in the Russian population. In the native population of Sakha (Yakutia) SLCO1B1 polymorphism was TT – 62 (82%), TC – 11 (14%), CC – 3 (4%) (Hardy–Weinberg’s chi-square test was 5.13 P=0.077). In comparison with data from Brazil, France, the People’s Republic of China, and Japan, C-allele frequency in the Sakha (Yakutian) population was not significantly different.ConclusionThus, we have studied the incidence of pathologic SLCO1B1 c.521C-allele in Russian and Sakha hyperlipidemic patients. The presence of SLCO1B1 C-allele in patients with hyperlipidemia forces us to be more careful in hypolipidemic drug prescription, especially statins, according to a higher risk of statin-induced myopathy development. The fact that SLCO1B1 C-allele is rarer among Sakha patients, could be interesting from the point of studying adverse drug effects frequency and statins’ effectiveness.

Frequency of Single Nucleotide Polymorphisms of the <i>SLCO1B1</i> Gene in Slavic Population of Central Europe

“…Compared to Slovak population, we determined significantly lower frequency only in Brazilian population (Santos et al, 2012). The incidence of SNP c.521T>C in Slovak population (23%) was slightly higher than in compared population of Caucasian and non-Caucasian origin, except for Russian (Sychev et al, 2016), where a similar frequency (22%) was observed.…”

Comparison of <em>CYP2C9</em>, <em>CYP2C19</em>, <em>CYP2D6</em>, <em>ABCB1</em>, and <em>SLCO1B1</em> gene-polymorphism frequency in Russian and Nanai populations

“…Studying the carriage of mutant alleles in different populations seems to be up to date, as far as optimization of the implementation of pharmacogenetic testing in clinical practice in different regions of Russia is concerned. Today, we have some data about the existence of polymorphisms in the Yakut population, a large ethnic group living in the Asian part of Russia; it is known that the frequency of CYP2C19*2 is 18.1%, CYP2C19*3 3.1%, CYP2C9*2 5.1%, CYP2C9*3 6.7%, SLCO1B1*5 14%, and VKORC1 G1639A 83.2% 14,15. Tatars and Bashkirs, ethnic groups living in the European part of Russia, have frequencies of CYP2C9*2 of 5.1% and 6%, CYP2C9*3 of 5.4% and 6.2%, and CYP2D6*4 of 9.5% and 7.1%, respectively 16,17.…”

“… 28 Patients from Moscow with hyperlipidemia were included by the SLCO1B1*5 T521C polymorphism, with χ 2 by Hardy–Weinberg of 2.8 ( P =0.09). 15 …”

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

“…Moscow / Москва *¹ [65] Moscow / Москва *² [66] Moscow / Москва [67] Moscow / Москва ³ [68] Laks / Лакцы [22] Dargins / Даргинцы [22] Avars / Аварцы [22] Russians / Русские 4 [69] Nanais / Нанайцы [23] Population / Популяция Prevalence / Распространенность (%) Figure 8. Ryazan / Рязань *¹ [72] Yaroslavl / Ярославль *² [73] Nanais / Нанайцы [23] Russians / Русские ³ [74] Avars / Аварцы [22] Yakuts / Якуты [20] Yakuts / Якуты 4 [74] Dargins / Даргинцы [22] Laks / Лакцы [22] Population / Популяция Prevalence / Распространенность (%) Figure 9. A. Rozhkov и соавт.…”

“…9. Имеются данные по частоте распространенности аллельного варианта SLCO1B1 +521T>C среди русских [72], якутов [72,73], нанайцев [23], лакцев, аварцев и даргинцев [22]. А. Хохлов и соавт.…”