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. 2014 Jun;17(6):441-7.

Frequencies of two functionally significant SNPs and their haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in six ethnic groups of Pakistani population

Tausif Ahmed Rajput  1 , Abdul Khaliq Naveed  1 , Shakir Khan  1 , Zia-Ur-Rehman Farooqi  1
Affiliations

Frequencies of two functionally significant SNPs and their haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in six ethnic groups of Pakistani population

Tausif Ahmed Rajput et al. Iran J Basic Med Sci. 2014 Jun.

Abstract

Objectives: Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by solute carrier organic transporter 1B1 (SLCO1B1) gene; a transporter involved in the uptake of drugs and endogenous compounds is present in hepatocyte sinusoidal membrane. Aim of this study was to investigate the frequencies of functionally significant SNPs (388A>G and 521T>C) and their haplotypes in 6 ethnic groups of Pakistani population through the development of rapid and efficient Tetra amplification refractory mutation system (T. ARMS) genotyping assay.

Materials and methods: Frequencies of alleles, genotype, and haplotypes of two functionally significant Single nucleotide polymorphism in 180 healthy Pakistani subjects and distributions in six ethnic groups by using a single step T. ARMS genotyping assay.

Results: The allelic frequency for 388A>G SNP was 50% in total Pakistani population with Single nucleotide polymorphism distributions of 9.7%, 15.1%, 19.4%, 16.1%, 18.3%, and 21.5% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri and Hazara/Baltistan groups respectively; and for 521T>C SNP it was 23.9% in total Pakistani population with distributions of 11.1%, 8.9%, 15.6%, 11.1%, 31.1% and 22.2% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri, and Hazara/Baltistan groups. Both functionally significant SNPs occurred in four major haplotypes with a frequency of 35.5% for 388A/521T (*1A), 40.5% for 388G/521T (*1B), 14.4% for 388A/521C (*5), and 9.4% for 388G/521C (*15) with varying distributions among six ethnic groups.

Conclusion: The 388A>G and 521T>C genotypes and corresponding haplotypes are present at varying frequencies in various ethnic groups of Pakistani population. Pharmacokinetic and pharmacodynamic profiling is needed to assess and characterize the effects of these haplotypes in our population.

Keywords: Haplotype; OATP1B1; SLCO1B1; Single nucleotide polymorphism.

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Figures

Figure 1
Figure 1
Results of Agarose gel electrophoresis for OATP1B1 N130D (388A>G) Lanes 1 and 2 indicate AA genotype comprising 346 bp Tetra ARMS control and 188 bp AA fragment. Lane 3 indicates GG genotype comprising 346 bp Tetra ARMS control and 212 bp GG fragment. Lane 4 indicates AG genotype comprising 346 bp Tetra ARMS control, 188bp A fragment and 212 bp G fragment
Figure 2
Figure 2
Results of agarose gel electrophoresis for OATP1B1 V174A (521T>C) Lane 1 indicates TT genotype comprising 359bp Tetra ARMS control and 223 bp TT fragment. Lanes 2 and 3 indicate TC genotype comprising 359 bp Tetra ARMS control, 223 bp T fragment, and 190 bp C fragment. Lane 4 indicates CC genotype comprising 359 bp Tetra ARMS control and 190 bp CC fragment
Figure 3
Figure 3
Frequency distribution of SLCO1B1 alleles and haplotypes within the ethnic groups of Pakistani population
See this image and copyright information in PMC

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