Marked differences in frequencies of statin therapy relevant SLCO1B1 variants and haplotypes between Roma and Hungarian populations

Abstract

BackgroundSLCO1B1 polymorphisms are relevant in statin pharmacokinetics. Aim of this study was to investigate the genetic variability and haplotype profile of SLCO1B1 polymorphisms in Roma and Hungarian populations. Genotypes of 470 Roma and 442 Hungarian subjects for c.388A > G, c.521T > C and c.1498-1331T > C polymorphisms were determined by PCR-RFLP assay. Using these SNPs eight different haplotypes could be differentiated.ResultsDifferences were found between Roma and Hungarians in SLCO1B1 388AA (24.5 vs. 45.5 %), GG (33.4 vs. 17.9 %) genotypes, AG + GG (75.5 vs. 54.5 %) carriers, in G allele frequency (0.545 vs. 0.362), respectively (p < 0.001). The most common SLCO1B1 haplotype was the ht8 (GTT) both in Roma (43.6 %) and in Hungarian (59.1 %) samples. The ht6 (GCT) was not present in Roma population samples Haplotype analyses showed striking differences between the Roma and Hungarian samples in ht4 (ATT, 37.2 % vs 20.8 %), ht5 (GCC, 1.15 % vs. 3.62 %) and ht8 (GTT, 43.6 % vs. 59.1 %) haplotypes (p < 0.01), respectively. Linkage disequilibrium analysis showed that the studied variants are in different linkage disequilibrium patterns depending on the ethnic origin.ConclusionsSimilarly to Caucasians the 388G is the minor allele in Hungarians, however, in Roma the 388A was found to be the minor allele contrary to Indians (India). The minor allele frequency of 521T > C and 1498-1331T > C SNPs are almost three times higher in Romas than in Indians (Singapore and Gujarati, respectively). Observed allele frequency for 1498-1331T > C polymorphism reflects the measured average European rates in Hungarians. The results can be applied in population specific treatment algorithms when developing effective programs for statin therapy.

Lack of association between SLCO 1B1 polymorphisms and lipid‐lowering response to simvastatin therapy in Thai hypercholesterolaemic patients

“…In this study, the allele frequency of the SLCO1B1 c.388A>G polymorphism was 74.9%. Our results were similar to Chinese hyperlipidemic patients (72.1%) and Han Chinese (73.4%) population, but lower than that of Singapore Chinese (79.5%) and Singapore Malays (87.0%) populations, and higher than that of Brazilian (32%), Hungarian (36.2%), German (36.5%), Greek (43.3%), North Indian (45.0%), Finnish (46.2%), Turkish (46.3%), Roma (54.5%), Chilean (54.7%) and Singapore Indian (57.0%) populations.…”

“…The allele frequency of SLCO1B1 c.521T>C polymorphism in hypercholesterolaemic patients in the present study (11.8%) was close to that of Singapore Malays (11%), Brazilian (12%) and Turkish (12.2%), but higher than that of African (5.7%) and Singapore Indian (6.5%) populations, and lower than that of English (13.0%), Singapore Chinese (13%) and Chilean (13.6%) populations, Han Chinese (14%), Brazilian (14%), Caucasian (14.8%), Mulatto (14.9%), German (15.0%), Chinese (16.2%), Greek (16.3%), Roma (17.2%), Hungarian (18.9%), Finnish (20.2%) and Amerindian (28.3%) populations . The g.89595T>C variant allele in this study (37.2%) was similar to that of Japanese (Tokyo) (39.4%) subjects, but higher than that of Indian (6.4%), Mexican (10.5%), African (10.8%), Nigeria (13.6%), Caucasian (15.4%), Kenya (15.1‐18.3%), Mulatto (18.2%), Roma (18.5%), Hungarian (19.6%), African (USA) (21.1%), Italian (22.5%) and Amerindians (26.1%) populations, and lower than that of Chinese (45.2%‐48.1%) population …”

“…The two common non‐synonymous SLCO1B1 polymorphisms, c.388A>G (p.Asn130Asp, rs2306283) and c.521T>C (p.Val174Ala, rs4149056), have been found to increase and decrease the transport activity of OATP1B1, respectively . These polymorphisms have been reported to affect the responses to statin therapy . Nevertheless, the association of these polymorphisms and lipid‐lowering responses was inconsistent among various studies .…”

“…It could be suggested that SLCO1B1 g.89595T>C polymorphism may affect the efficacy of the statin treatment. And the linkage disequilibrium between g.89595T>C and c.521T>C polymorphisms may be different among ethnicities . The association between SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms and lipid‐lowering response to statin therapy in the Thai population has not been yet elucidated.…”

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

“…SLCO1B1 gene is located on chromosome 12 (12p12.1), and the 388A>G (rs2306283) and 521T>C (rs4149056) are two common single nucleotide polymorphisms (SNPs) which can form four haplotypes, including SLCO1B1 *1a (388A‐521T), SLCO1B1 *1b (388G‐521T), SLCO1B1 *5 (388A‐521C), and SLCO1B1 *15 (388G‐521C). The SLCO1B1 *5 and SLCO1B1 *15 haplotypes (carriers of 521C allele) are associated with reduced activity of OATP1B1 transportation …”