Multiplex allele-specific PCR to determine genotypes at statin metabolizing SNP loci- rs1135840 and rs776746

  • Abu Ashfaqur Sajib Associate Professor, Department of Genetic Engineering & Biotechnology, University of Dhaka
  • Raka Aziz
  • Shayan Shariar
  • Abira Khan
  • Sharif Akhteruzzaman
Keywords: rs1135840, CYP2D6, rs776746, CYP3A5, Allele Specific PCR, Statins, Diabetes

Abstract

Single nucleotide polymorphisms (SNPs) play crucial roles in determining the extent of susceptibility to various diseases as well as actions of proteins involved in drug metabolism and transport. Statins are the first-line drugs for lowering cholesterol level and one of the commonly prescribed classes of drugs to patients with cardiovascular diseases (CVD). CVDs are the most prevalent cause of co-morbidity and mortality among patients with diabetes. Multiple studies have reported the diabetogenic effect of statins. rs1135840 and rs776746 are two SNPs that affect statin metabolism and consequently increase their concentration in the blood. We have developed a simple, reliable and cost-effective allele specific PCR (AS-PCR) based method to determine the genotypes at rs1135840 and rs776746 loci and applied to calculate the allele and genotypic frequencies in Bangladeshi population. Both rs1135840 and rs776746 variant alleles are present at high frequencies (0.43 and 0.36, respectively) in Bangladeshi population. Although the percentage of homozygous rs776746 variant genotype is relatively low (7.0%) in Bangladeshi population, homozygous rs1135840 variant frequency is quite high (22.0%). On the other hand, 21.94% and 2.55% of the Bangladeshi individuals are heterozygous and homozygous, respectively, for both variant alleles. The AS-PCR method described here may be used to optimize the dose of statin guided by an individual’s genotype and, therefore, increase the efficacy of statin treatment.

Published
2019-10-12
Section
Articles