Frequencies of two functionally significant SNPs and their haplotypes of organic anion transporting polypeptide ۱B۱ SLCO۱B۱ gene in six ethnic groups of Pakistani population

Objective(s):Organic anion transporter polypeptide ۱B۱ (OATP۱B۱) encoded by solute carrier organic transporter ۱B۱ (SLCO۱B۱) 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 (۳۸۸A>G and ۵۲۱T>C) and their haplotypes in ۶ 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 ۱۸۰ healthy Pakistani subjects and distributions in six ethnic groups by using a single step T. ARMS genotyping assay. Results: The allelic frequency for ۳۸۸A>G SNP was ۵۰% in total Pakistani population with distributions of ۹.۷%, ۱۵.۱%, ۱۹.۴%, ۱۶.۱%, ۱۸.۳%, and ۲۱.۵% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri and Hazara/Baltistan groups respectively; and for ۵۲۱T>C SNP it was ۲۳.۹% in total Pakistani population with distributions of ۱۱.۱%, ۸.۹%, ۱۵.۶%, ۱۱.۱%, ۳۱.۱% and ۲۲.۲% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri, and Hazara/Baltistan groups. Both functionally significant SNPs occurred in four major haplotypes with a frequency of ۳۵.۵% for ۳۸۸A/۵۲۱T (*۱A), ۴۰.۵% for ۳۸۸G/۵۲۱T (*۱B), ۱۴.۴% for ۳۸۸A/۵۲۱C (*۵), and ۹.۴% for ۳۸۸G/۵۲۱C (*۱۵) with varying distributions among six ethnic groups. Conclusion: The ۳۸۸A>G and ۵۲۱T>C genotypes and corresponding haplotypes are present at varying frequencies in various ethnic groups of Pakistani population. Pharmacokinetic and pharmacodynamic

Keywords:

Haplotype , OATP۱B۱ , single nucleotide polymorphism , SLCO۱B۱