Statins and the Pharmacogenetic Basis of Their Adverse Effects. An Investigation on Bangladeshi Hyperlipidemics

Although there is a high frequency of statin use in Bangladesh, the genetic basis of statin-related toxicities in native population is largely unknown. Since COQ2 gene is involved in the same pathway as statin’s mechanism of action and alterations in TNF alpha gene are found to be related to different adverse effects on human body, we hypothesized that genetic variation in COQ2 (rs4693075) and TNF alpha (rs1799724) genes would be associated with inter-individual variation in statin intolerance. We used the PCR-RFLP method to investigate a total of 151 subjects, among whom 57 were those who developed toxicity on statin monotherapy and the rest 94 tolerated statins without any incident or complaint. Our result showed one significant correlation between polymorphism in COQ2 gene and statin intolerance. The Odds ratio (with 95% confidence intervals) for increased risk of statin intolerance among homozygotes for the rare alleles was 2.2564 (1.0578 to 4.8131), with a P value of 0.0353. These preliminary results are consistent with the notion that statin intolerance which is initiated through muscle symptoms is associated with genomic variation in COQ2.