Method for predicting statin response: combination of two CYP7A1 variants
TS-038888 — A model to predict CYP7A1 activity and individual response to statins.
Cholesterol 7α-hydroxylase (CYP7A1) is an enzyme that catalyzes the first and the rate-limiting step in the biosynthesis of bile acid from cholesterol and serves as a main pathway for cholesterol removal from the body. CYP7A1 plays an important role in lipid metabolism and the development of…
Cholesterol 7α-hydroxylase (CYP7A1) is an enzyme that catalyzes the first and the rate-limiting step in the biosynthesis of bile acid from cholesterol and serves as a main pathway for cholesterol removal from the body. CYP7A1 plays an important role in lipid metabolism and the development of cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in the CYP7A1 gene have been associated with variance in lipid levels and risks of cardiovascular diseases; however, results are inconsistent, and causative SNPs remain uncertain.
Researchers at he Ohio State University have recently identified a novel enhancer SNP downstream of the CYP7A1 promoter that affects enhancer activity. They found that the combination of this enhancer with the previously identified promoter SNP profoundly affects CYP7A1 expression in human liver. Therefore, they developed a 2-SNP model predictive of CYP7A1 activity and associations with clinical phenotypes. Their model reflects varying allele frequencies and linkage disequilibrium between the two SNPs. The SNPs interact in complex ways, which leads to a failure to detect clinical associaitons and conflicting study results.
The CYP7A1 2-SNP marker can be used to predict statin response and risk of side effects. Individuals with high CYP7A1 activity status should use alternative therapy, instead of relying on increasing statin dose, for better cholesterol control and reduction of side effects such as statin-induced myopathy and diabetes.
- Predictive models
- Personalized medicine
- Significant associations with lipid levels, statin response, cardiovascular diseases and diabetes.
- A 2-SNP model of CYP7A1 variants could be used to guide statin treatment in cardiovascular patients