Interactions between CYP7A1 A-204C and ABCG8 C1199A polymorphisms on lipid lowering with atorvastatin

What is known and Objective: Cholesterol excretion by ATP binding cassette transporters G5 and G8 (ABCG5/G8) and bile acid biosynthesis by 7a‐hydroxylase (CYP7A1) are major pathways for the removal of cholesterol into bile. This suggests that variations in the CYP7A1 and ABCG8 genes may influence the statin response. We aimed to investigate the effect of CYP7A1 A‐204C and ABCG8 C1199A polymorphisms and their interactions on the lipid‐lowering response to atorvastatin in a Chinese population. Methods: Genotypes were determined by using polymerase chain reaction‐restrict fragment length polymorphism (PCR‐RFLP) in 185 hyperlipidaemic patients treated with atorvastatin, 20 mg once daily for 4 weeks. Serum levels of triglycerides (TGs), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), and high‐density lipoprotein cholesterol (HDL‐C) were determined before and after treatment. Results and Discussion: For 181 patients (89 males), variant allele frequencies of CYP7A1 ‐204C and ABCG8 1199A were 0·347 and 0·128, respectively. Among all patients, homozygotes for the ‐204A allele showed a slightly significant mean percentage reduction from baseline in TG level after treatment than heterozygotes and homozygotes for the ‐204C allele (?25·49 ± 8·12%vs. ?22·80 ± 8·72%, P = 0·054, and ?25·49 ± 8·12%vs.?22·51 ± 8·82%, P = 0·048, respectively). For patients with the ABCG8 C1199A variant allele, the difference in percentage reduction from baseline in TG level was increased between the CYP7A1 A‐204C wild‐type allele homozygotes and variant allele homozygotes after atorvastatin treatment (?28·35%vs.?19·28%, P = 0·001), and increased differences were found between the CYP7A1 A‐204C wild‐allele homozygotes and variant allele homozygotes (?18·95%vs.?15·61%, P = 0·009) and between the CYP7A1 A‐204C variant allele heterozygotes and homozygotes (?18·69%vs.?15·61%, P = 0·012, respectively). What is new and Conclusion: The CYP7A1 ‐204A and ABCG8 1199A alleles appear to interact to affect lipid‐lowering response to atorvastatin. However, given the relatively small number of subjects with the influential variant allele combinations, and the heterogeneity in response, even in the selected sub‐populations, testing would be of little clinical utility in the Chinese population sampled.