Frequencies of Single-Nucleotide Polymorphisms and Haplotypes of the SLCO1B1 Gene in Selected Populations of the Western Balkans

Abstract

As a membrane influx transporter, organic anion-transporting polypeptide 1B1 (OATP1B1) regulates the cellular uptake of a number of endogenous compounds and drugs. The aim of this study was to characterize the diversity of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encoding this transporter in two ethnic groups populating the Western Balkans. The distribution of SCLO1B1 alleles was determined at seven variant sites (c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G) in 266 Macedonians and 94 Albanians using the TaqMan allelic discrimination assay. No significant difference in the frequencies of the single nucleotide polymorphisms (SNPs) was observed between these populations. The frequency of the c.521T>C SNP was the lowest (<13.7 and 12.2%, respectively), while the frequencies of all other SNP alleles were above 40.0%. Variant alleles of c.1463G>C and c.1086 C>T SNPs were not identified in either ethnic group. The haplotype analysis revealed 20 and 21 different haplotypes in the Macedonian and Albanian population, respectively. The most common haplotype in both ethnic groups, *1J/*1K/*1L, had a frequency of 39.0% and 26.6%, respectively. In both populations, the variant alleles of the functionally significant c.521T>C and c.388A>G SNPs existed in one major haplotype (*15/*16/*17), with a frequency of 8.6 and 2.4% in the Macedonian and Albanian subjects, respectively. In conclusion, sequence variations of the SLCO1B1 gene in the studied populations occur at high frequencies, which are similar to that of the Caucasian population. Further studies are needed to evaluate the clinical significance of these SNPs and/ or the major SLCO1B1 haplotypes they form for a large number of substrates and for susceptibility to certain diseases.

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

“…On the other hand, the minor allele frequency of c.521C was almost half less (23%) than 388G allele. When comparing our data with published studies, the most often occurring SNP c.388A>G in our studied population had a similar allelic frequency in German (Mwinyi et al, 2008), Hungarian (Nagy et al, 2015), Macedonian, Albanian (Grapci et al, 2015) and…”

“…These populations have different origin than Slovak population. We also found out difference in Macedonians, Albanians (Grapci et al, 2015), Greeks (Giannakopoulou et al, 2014) compare to Slovaks for c.521T>C. Macedonians belong to South Slavic ethnic group, Albanian and Greek have their origin in the Middle East. It was interesting to find statistically significant difference between Slovak and Finnish (Pasanen et al, 2006b) population for c.388A>G and between Slovak and German (Mwinyi et al, 2008) for c.521T>C, though all three ethnic populations belong to Caucasian population.…”

Increased risk of aspirin-induced gastric mucosal erosion in elderly Chinese men harboring SLCO1B1*1b/*1b while using aspirin and an ACEI or ARB concomitantly

“…ACEIs and ARBs are generally transported into human hepatocytes from portal blood to be metabolized, predominantly via OATP1B1 [17]. Among the mutations identified in the OATP1B1 coding gene ( SLCO1B ), A388G and T521C occur frequently and are common in the Chinese population (allelic frequencies 73 and 14%, respectively) [18]. There are four haplotypes: SLCO1B1*1a (wild type), SLCO1B1*1b , SLCO1B1*5 and SLCO1B1*15 , and the SLCO1B1*1b/*1b (GT/GT) and *1a/*1b (AT/GT) diplotypes have been frequently reported in the Chinese population [19, 20].…”

Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions

“…In vivo, the SLCO1B1 c.521T>C polymorphism is associated with increased risk of simvastatin-induced myopathy [ 40 ]. The SNP c.521T>C (p.Val174Ala) is more common in European-Americans (allelic frequency 14% [ 39 ]) and Asian (allelic frequency 10–15% [ 41 ]) populations. This genetic polymorphism was reported to increase the plasma exposure of atorvastatin and rosuvastatin in 32 healthy white subjects [ 42 ].…”