Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Clinical and Laboratory Measurements
2.3. Metabolomics Analysis
2.4. Genotyping
2.5. Statistical Analysis
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical and Laboratory Characteristics | Participants without Statin Treatment | Participants on Simvastatin Treatment | p * | ||||
---|---|---|---|---|---|---|---|
rs4149056 TT (n = 814) | rs4149056 CC + CT (n = 554) | rs4149056 TT (n = 841) | rs4149056 CC + CT (n = 532) | ||||
Mean ± SD | Mean ± SD | p | Mean ± SD | Mean ± SD | p | ||
Age (years) | 59.65 ± 6.74 | 58.81 ± 7.04 | 0.028 | 59.53 ± 7.1 | 59.67 ± 7.14 | 0.707 | 0.046 |
Body mass index (kg/m2) | 27.32 ± 3.73 | 27.13 ± 3.85 | 0.300 | 27.29 ± 3.74 | 27.51 ± 4.11 | 0.387 | 0.112 |
Waist (cm) | 98.51 ± 10.43 | 97.57 ± 10.37 | 0.096 | 98.81 ± 10.55 | 99.31 ± 11.03 | 0.430 | 0.007 |
Systolic blood pressure (mmHg) | 140.99 ± 16.77 | 140.9 ± 16.82 | 0.907 | 137.5 ± 16.16 | 138.66 ± 15.34 | 0.143 | 0.022 |
Fasting plasma glucose (mmol/L) | 5.66 ± 0.51 | 5.63 ± 0.49 | 0.309 | 5.78 ± 0.47 | 5.80 ± 0.49 | 0.336 | 3.5 × 10−9 |
2 h plasma glucose (mmol/L) | 6.14 ± 1.7 | 6.06 ± 1.76 | 0.329 | 6.46 ± 1.74 | 6.35 ± 1.75 | 0.265 | 0.005 |
LDL cholesterol (mmol/L) | 3.62 ± 0.8 | 3.59 ± 0.79 | 0.522 | 2.68 ± 0.72 | 2.74 ± 0.71 | 0.133 | 9.1 × 10−66 |
Total triglycerides (mmol/L) | 1.41 ± 0.78 | 1.52 ± 1.79 | 0.365 | 1.41 ± 0.73 | 1.43 ± 0.73 | 0.360 | 0.320 |
ALT (U/L) | 29.21 ± 17.63 | 29.32 ± 22.24 | 0.616 | 32.29 ± 18.06 | 32.89 ± 16.69 | 0.385 | 0.003 |
Fasting plasma insulin (mU/L) | 8.55 ± 6.31 | 8.0 ± 5.53 | 0.067 | 9.53 ± 6.98 | 9.42 ± 6.57 | 0.870 | 0.0001 |
Fasting plasma proinsulin (pmol/L) | 13.88 ± 6.92 | 13.43 ± 6.1 | 0.241 | 15.04 ± 7.49 | 14.85 ± 7.52 | 0.454 | 0.0006 |
hS-CRP (mg/L) | 2.42 ± 3.22 | 2.57 ± 3.66 | 0.145 | 1.99 ± 3.87 | 1.72 ± 2.18 | 0.825 | 5.0 × 10−06 |
Matsuda ISI comp (mg/dL. mU/L) | 6.9 ± 4.28 | 7.34 ± 4.41 | 0.061 | 5.74 ± 3.58 | 5.73 ± 3.37 | 0.776 | 3.0 × 10−11 |
Disposition index | 162.05 ± 76.56 | 167.35 ± 88.51 | 0.228 | 154.15 ± 66.96 | 153.99 ± 65.18 | 0.818 | 0.005 |
No Statin | Simvastatin | Novel (Ref.) | |||||
Metabolite | Beta | p | Beta | p | Subclass | p comp | |
21-hydroxypregnenolone monosulfate (1) | 0.211 | 1.9 × 10−6 | 0.112 | 0.003 | Pregnenolone Steroids | 0.008 | Yes |
Docosadioate (C22-DC) | 0.110 | 4.7 × 10−5 | 0.025 | 0.351 | Fatty Acid, Dicarboxylate | 0.026 | Yes |
Dodecanedioate (C12-DC) | 0.115 | 1.9 × 10−5 | 0.012 | 0.659 | Fatty Acid, Dicarboxylate | 0.006 | Yes |
Comparison between statistically significant associations of SLCO1B1 rs4149056-C with metabolites in participants with simvastatin treatment (n = 1368) and not statistically significant in participants with simvastatin treatment (n = 1373) | |||||||
No Statin | Simvastatin | ||||||
Metabolite | Beta | p | Beta | p | Subclass | p comp | |
Glycoursodeoxycholic acid sulfate (1) | 0.036 | 0.307 | 0.174 | 1.4 × 10−7 | Secondary Bile Acid Metabolism | 0.0003 | Yes |
1-palmitoleoyl-GPC (16:1) | 0.029 | 0.280 | 0.111 | 3.5 × 10−5 | Lysophospholipid | 0.031 | No (16) |
Comparison between statistically significant associations of SLCO1B1 rs4149056-C with metabolites in participants without statin treatment (n = 1368) and in participants with simvastatin treatment (n = 1373) | |||||||
No Statin | Simvastatin | ||||||
Metabolite | Beta | p | Beta | p | Subclass | p comp | |
Glycocholenate sulfate | 0.352 | 4.1 × 10−41 | 0.416 | 1.4 × 10−58 | Secondary Bile Acid Metabolism | 0.049 | No (16.35) |
GlcNAc sulfate conjugate of C21H34O2 steroid | 0.293 | 1.2 × 10−18 | 0.389 | 8.2 × 10−36 | Partially Characterized Molecules | 0.005 | Yes |
1-linoleoyl-GPG (18:2) | 0.189 | 1.8 × 10−8 | 0.284 | 2.5 × 10−22 | Lysophospholipid | 0.009 | Yes |
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Fernandes Silva, L.; Ravi, R.; Vangipurapu, J.; Oravilahti, A.; Laakso, M. Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment. Metabolites 2022, 12, 1159. https://doi.org/10.3390/metabo12121159
Fernandes Silva L, Ravi R, Vangipurapu J, Oravilahti A, Laakso M. Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment. Metabolites. 2022; 12(12):1159. https://doi.org/10.3390/metabo12121159
Chicago/Turabian StyleFernandes Silva, Lilian, Rowmika Ravi, Jagadish Vangipurapu, Anniina Oravilahti, and Markku Laakso. 2022. "Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment" Metabolites 12, no. 12: 1159. https://doi.org/10.3390/metabo12121159