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

BMC Genetics

Bela Melegh²  Kalman Toth³  Alma Ganczer¹  Petra Matyas¹  Bela Imre Melegh¹  Renata Szalai²  Csilla Sipeky²  Agnes Nagy³ 

[1] Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti 12, Pecs, H-7624, Hungary;Janos Szentagothai Research Centre, Human Genetic and Pharmacogenomic Research Group, University of Pecs, Pecs, Hungary;1st Department of Internal Medicine, University of Pecs, Pecs, Hungary

关键词: Pharmacogenetics;    Hungarian;    Roma;    Haplotype;    Statin;    SLCO1B1;   

Others  :  1224622
DOI  :  10.1186/s12863-015-0262-4

 received in 2015-06-04, accepted in 2015-08-12,  发布年份 2015

【 摘 要 】

Background

SLCO1B1 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.

Results

Differences 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.

Conclusions

Similarly 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.

【 授权许可】

   
2015 Nagy et al.

【 图 表 】

Fig. 1.

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