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. 2015;16(5):449-58.
doi: 10.2217/pgs.15.2.

SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization

Josephine H Li  1 , Sunil Suchindran, Svati H Shah, William E Kraus, Geoffrey S Ginsburg, Deepak Voora
Affiliations

SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization

Josephine H Li et al. Pharmacogenomics. 2015.

Abstract

Aim: SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients.

Patients & methods: In high-risk Caucasians undergoing cardiac catheterization, we tested the association between rs4149056/625T>C and rs2306283/492A>G with low-density lipoprotein cholesterol (LDL-c) over 3 years (n = 1402) and death/MI over 6 years (n = 2994), accounting for statin use or type during follow-up.

Results: Carriers of the rs4149056 C allele had 6.2 ± 1.7 mg/dl higher LDL-c per C allele (p < 0.001) but were not at higher risk for death/MI (p = 0.9). We found no associations between rs2306283 and LDL-c or death/MI (p > 0.6).

Conclusion: Functional SLCO1B1 variants are not associated with death/MI in patients commonly treated with statins, despite higher LDL-c in carriers of the rs4149056 C allele.

Keywords: SLCO1B1; cardiovascular events; low-density lipoprotein cholesterol; myocardial infarction; pharmacogenetics; rs2306283; rs4149056; statin.

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Figures

Figure 1
Figure 1. Number of individuals included in the primary analyses examining the association between genotypes and death/myocardial infarction, and the association between genotypes and LDL-c levels
LDL-c: Low-density lipoprotein cholesterol; MI: Myocardial infarction.
Figure 2
Figure 2. Association of rs4149056 with low-density lipoprotein cholesterol levels
Displayed are means and standard errors of LDL-c levels by rs4149056 genotype. Levels of significance were obtained using linear mixed models for an additive model, adjusted for subject-reported statin utilization and time. Per C allele, there was a ~5% higher LDL-c over a 3-year follow-up period. LDL-c: Low-density lipoprotein cholesterol.
Figure 3
Figure 3. Association of rs4149056 with low-density lipoprotein cholesterol, stratified by statin type
Displayed are means and standard errors of LDL-c levels by rs4149056 genotype and statin type. ‘Other statin’ was composed of 46.4% pravastatin, 30.4% rosuvastatin, 17.9% lovastatin and 5.3% fluvastatin. An interaction term assessed homogeneity of genotype effects on LDL-c by statin type. Due to the analysis, statin type subgroups contained overlapping individuals. There was no evidence for rs4149056 genotype by statin type interaction. LDL-c: Low-density lipoprotein cholesterol.
Figure 4
Figure 4. Association of rs2306283 with low-density lipoprotein cholesterol levels
Displayed are means and standard errors of LDL-c levels by rs2306283 genotype. Levels of significance were obtained using linear mixed models for an additive model, adjusted for subject-reported statin utilization and time. There was no association between rs2306283 and LDL-c levels. LDL-c: Low-density lipoprotein cholesterol.
Figure 5
Figure 5. Association of rs2306283 with low-density lipoprotein cholesterol, stratified by statin type
Displayed are means and standard errors of LDL-c levels by rs2306283 genotype and statin type. ‘Other statin’ was composed of 46.4% pravastatin, 30.4% rosuvastatin, 17.9% lovastatin and 5.3% fluvastatin. An interaction term assessed homogeneity of genotype effects on LDL-c by statin type. Due to the analysis, statin type subgroups contained overlapping individuals. There was no evidence for rs2306283 genotype by statin type interaction. LDL-c: Low-density lipoprotein cholesterol.
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