Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

Abstract

SUMMARY:In this study we evaluated the possible association between five single nucleotide polymorphisms in ABCG5 (rs6720173) and ABCG8 (rs11887534, rs4148211, rs4148217 and rs6544718) genes and ezetimibe response in Chilean hypercholesterolemic subjects. A total of 60 non-related hypercholesterolemic subjects, aged 18 to 65 years old were included in this study. These subjects were treated with ezetimibe (10mg/day) during one month. The ABCG5 and ABCG8 genotypes were assessed by PCR-RFLP. The genotype distribution of the ABCG5/ABCG8 polymorphisms was in Hardy-Weinberg equilibrium. Our results showed that the investigated polymorphisms were not associated with the response to ezetimibe. Nevertheless, the T allele of rs6544718 polymorphism was related to higher baseline levels of LDL-cholesterol (p<0.001). In addition, the G allele for the rs4148211 polymorphism was associated with greater baseline concentrations of triglycerides (P=0.019). This allele was also associated with lower concentrations of HDL-cholesterol (P=0.027), after ezetimibe treatment. Our results suggest that the studied polymorphisms do not affect the therapeutic response to ezetimibe in the evaluated subjects.

An association of ABCG8: rs11887534 polymorphism and HDL-cholesterol response to statin treatment in the Polish population

“…Therefore, we are fully aware that our results should be interpreted with caution and need to be replicated using a larger sample size of patients qualified in randomized manner to the groups treated with CYP3A4-metabolized statins (simvastatin or atorvastatin), non-CYP3A4-metabolized statins (fluvastatin, pravastatin or rosuvastatin) or ezetimibe. Ezetimibe, a selective cholesterol absorption inhibitor blocking Niemann-Pick C1 like-1 (NPC1L1) protein, is effective in sitosterolemia caused by ABCG5/ABCG8 mutations but Caamano et al reported no association between ABCG8 : rs11887534 polymorphism and lipid response (including HDL changes) to treatment with ezetimibe [ 36 ]. On the other hand, Zsiros et al revealed that NPC1L1 : c.-133A > G polymorphism modifies the ApoA1 response to ezetimibe and therefore, rather than altering HDL concentration, may alter the effects of ezetimibe on the structure and function of HDL particles [ 37 ].…”