Grapci A Daka, Dimovski A J, Kapedanovska A, Vavlukis M, Eftimov A, Geshkovska N Matevska, Labachevski N, Jakjovski K, Gorani D, Kedev S, Mladenovska K
Faculty of Medicine, University "Hasan Prishtina", Blv. "Mother Theresa" NN, 10 000 Prishtina, Republic of Kosovo.
Faculty of Pharmacy, Center for Biomolecular Pharmaceutical Analyses, University "Ss Cyril and Methodius" in Skopje, Blv. "Mother Theresa" 47, 1000 Skopje, Republic of Macedonia.
Balkan J Med Genet. 2015 Dec 30;18(1):5-21. doi: 10.1515/bjmg-2015-0001. eCollection 2015 Jun.
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.
作为一种膜内流转运体,有机阴离子转运多肽1B1(OATP1B1)调节多种内源性化合物和药物的细胞摄取。本研究的目的是描述编码该转运体的溶质载体有机阴离子转运家族成员1B1(SLCO1B1)基因在西巴尔干地区两个民族中的多样性。使用TaqMan等位基因鉴别分析,在266名马其顿人和94名阿尔巴尼亚人的7个变异位点(c.388A>G、c.521T>C、c.571T>C、c.597C>T、c.1086C>T、c.1463G>C和c.439T>G)确定了SCLO1B1等位基因的分布。在这些人群中,未观察到单核苷酸多态性(SNP)频率的显著差异。c.521T>C SNP的频率最低(分别<13.7%和12.2%),而所有其他SNP等位基因的频率均高于40.0%。在这两个民族中均未鉴定出c.1463G>C和c.1086 C>T SNPs的变异等位基因。单倍型分析分别在马其顿和阿尔巴尼亚人群中揭示了20种和21种不同的单倍型。两个民族中最常见的单倍型1J/*1K/*1L的频率分别为39.0%和26.6%。在这两个人群中,功能上重要的c.521T>C和c.388A>G SNPs的变异等位基因存在于一个主要单倍型(*15/*16/*17)中,在马其顿和阿尔巴尼亚受试者中的频率分别为8.6%和2.4%。总之,研究人群中SLCO1B1基因的序列变异发生频率较高,与白种人群相似。需要进一步研究来评估这些SNP和/或它们形成的主要SLCO1B1单倍型对大量底物和某些疾病易感性的临床意义。