SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals

Abstract

The use of statins as the preferred lipid-lowering therapy has clearly demonstrated its efficacy in the treatment of hypercholesterolemia, reducing also the risk of coronary events and cardiovascular disease mortality. In this study, we assessed single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene and their effect on atorvastatin response. We included 129 Chilean hypercholesterolemic patients undergoing 10 mg/day of atorvastatin therapy during 4 weeks. Lipid profile was determined before and after drug administration. Genotyping of SLCO1B1 rs4149056 (c.521T>C) SNP was performed with allele-specific polymerase chain reaction, whilst polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the SLCO1B1 rs2306283 (c.388A>G) variant. After statin therapy, concentrations of TC, LDL-C and TG had a decrease from baseline (p < 0.05). Also, HDL-C levels increased (p < 0.05). Minor allele frequencies for the rs2306283 and rs4149056 variants were 0.547 and 0.136, respectively. LDL-C response to atorvastatin was not associated with the SLCO1B1 rs4149056 nor the rs2306283 polymorphisms (p > 0.05). However, the latter SNP was associated with HDL-C variability after atorvastatin medication (p = 0.02). This study indicates that LDL-C reduction following atorvastatin therapy is not influenced by the SNPs evaluated. In addition, the polymorphism rs2306283 at the SLCO1B1 gene determines greater HDL-C concentrations in response to atorvastatin medication in Chilean hypercholesterolemic subjects.

Lack of association between SLCO 1B1 polymorphisms and lipid‐lowering response to simvastatin therapy in Thai hypercholesterolaemic patients

“…There was no association between SLCO1B1 c.521T>C variant and lipid‐lowering response to 3 and 12 months of 20 or 40 mg/day simvastatin therapy in the present study. Our results agree with the Chilean and Brazilian populations, in which no association between the c.521T>C and changes in lipid parameters after 4 weeks administration of 10 mg/day of atorvastatin was observed . Similarly, there was no association between c.521T>C genotypes and the therapeutic effect of pitavastatin (2 mg/day, 8 weeks) in Chinese patients .…”

“…In this study, the allele frequency of the SLCO1B1 c.388A>G polymorphism was 74.9%. Our results were similar to Chinese hyperlipidemic patients (72.1%) and Han Chinese (73.4%) population, but lower than that of Singapore Chinese (79.5%) and Singapore Malays (87.0%) populations, and higher than that of Brazilian (32%), Hungarian (36.2%), German (36.5%), Greek (43.3%), North Indian (45.0%), Finnish (46.2%), Turkish (46.3%), Roma (54.5%), Chilean (54.7%) and Singapore Indian (57.0%) populations.…”

“…The allele frequency of SLCO1B1 c.521T>C polymorphism in hypercholesterolaemic patients in the present study (11.8%) was close to that of Singapore Malays (11%), Brazilian (12%) and Turkish (12.2%), but higher than that of African (5.7%) and Singapore Indian (6.5%) populations, and lower than that of English (13.0%), Singapore Chinese (13%) and Chilean (13.6%) populations, Han Chinese (14%), Brazilian (14%), Caucasian (14.8%), Mulatto (14.9%), German (15.0%), Chinese (16.2%), Greek (16.3%), Roma (17.2%), Hungarian (18.9%), Finnish (20.2%) and Amerindian (28.3%) populations . The g.89595T>C variant allele in this study (37.2%) was similar to that of Japanese (Tokyo) (39.4%) subjects, but higher than that of Indian (6.4%), Mexican (10.5%), African (10.8%), Nigeria (13.6%), Caucasian (15.4%), Kenya (15.1‐18.3%), Mulatto (18.2%), Roma (18.5%), Hungarian (19.6%), African (USA) (21.1%), Italian (22.5%) and Amerindians (26.1%) populations, and lower than that of Chinese (45.2%‐48.1%) population …”

“…Furthermore, our results were also consistent with Greek hypercholesterolaemic patients, in which there was no significant association between the c.388A>G and lipid‐lowering efficacy of simvastatin treatment. In contrast, significantly decreased LDL‐C and increased HDL‐C in response to 10 mg/day atorvastatin therapy in homozygous individuals for the 388G allele were observed in Brazilian and Chilean populations, respectively . In addition, the 388G allele carriers had increased TC and LDL‐C reduction in response to simvastatin in Brazilian population …”

“…The two common non‐synonymous SLCO1B1 polymorphisms, c.388A>G (p.Asn130Asp, rs2306283) and c.521T>C (p.Val174Ala, rs4149056), have been found to increase and decrease the transport activity of OATP1B1, respectively . These polymorphisms have been reported to affect the responses to statin therapy . Nevertheless, the association of these polymorphisms and lipid‐lowering responses was inconsistent among various studies .…”