Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Population
2.2. Biochemical Measurements
NMR Lipoprotein Parameter | Diameter Range (nm) |
---|---|
VLDL | |
Large VLDL/chylomicrons | >60 |
Medium VLDL | 35–60 |
Small VLDL | 27–35 |
LDL | |
Large LDL | 21.2–23 |
Small LDL | 18–21.2 |
HDL | |
Large HDL | 8.8–13 |
Medium HDL | 8.2–8.8 |
Small HDL | 7.3–8.2 |
2.3. Genotyping
2.4. Statistical Methods
3. Results
Age, year | 48.42 (16.34) | ||
Gender, % male | 48.28 | ||
Smoker, % current | 7.79 | ||
BMI | 28.25 (5.62) | ||
Baseline | Post-Fenofibrate | p | |
Small VLDL concentration, nmol/L | 32.93 (21.89) | 22.83 (15.83) | <0.0001 |
Medium VLDL concentration, nmol/L | 37.49 (36.74) | 18.46 (20.44) | <0.0001 |
Large VLDL concentration, nmol/L | 3.93 (7.68) | 2.09 (3.24) | <0.0001 |
VLDL total particles; nmol/L | 74.38 (50.81) | 43.41 (31.73) | <0.0001 |
VLDL diameter; nm | 51.39 (7.86) | 51.84 (8.71) | 0.14 |
Small LDL concentration, nmol/L | 925.64 (557.03) | 779.49 (373.04) | <0.0001 |
Large LDL concentration, nmol/L | 407.11 (272.91) | 397.23 (201.37) | 0.19 |
LDL total particles; nmol/L | 1375.33 (437.46) | 1209.35 (380.68) | <0.0001 |
LDL diameter; nm | 20.81 (0.88) | 20.90 (0.58) | <0.0001 |
Small HDL concentration, nmol/L | 21.65 (5.54) | 20.76 (6.71) | 0.003 |
Medium HDL concentration, nmol/L | 3.00 (3.61) | 5.92 (4.80) | <0.0001 |
Large HDL concentration, nmol/L | 6.32 (3.54) | 5.73 (3.25) | <0.0001 |
HDL total particles; nmol/L | 30.97 (5.63) | 32.42 (5.95) | <0.0001 |
HDL diameter; nm | 8.85 (0.45) | 8.73 (0.39) | <0.0001 |
Baseline fasting TG < 150 mg/dL (N = 544) | |||
Small VLDL concentration, nmol/L | 28.13 (15.67) | 18.60 (12.60) | <0.001 |
Medium VLDL concentration, nmol/L | 21.06 (14.68) | 12.34 (11.07) | <0.001 |
Large VLDL concentration, nmol/L | 1.39 (1.53) | 0.95 (1.22) | <0.001 |
VLDL total particles; nmol/L | 50.62 (24.01) | 31.92 (19.76) | <0.001 |
VLDL diameter; nm | 50.73 (8.20) | 51.12 (9.19) | 0.44 |
Small LDL concentration, nmol/L | 705.82 (403.85) | 662.38 (261.74) | <0.001 |
Large LDL concentration, nmol/L | 478.91 (252.68) | 398.55 (184.97) | <0.001 |
LDL total particles; nmol/L | 1213.23 (364.60) | 1073.37 (279.02) | <0.001 |
LDL diameter; nm | 21.14 (0.73) | 21.01 (0.53) | 0.001 |
Small HDL concentration, nmol/L | 20.53 (5.17) | 19.25 (6.08) | <0.001 |
Medium HDL concentration, nmol/L | 3.34 (3.54) | 6.67 (4.47) | <0.001 |
Large HDL concentration, nmol/L | 7.27 (2.30) | 6.42 (3.30) | <0.001 |
HDL total particles; nmol/L | 31.15 (5.18) | 32.35 (5.44) | <0.001 |
HDL diameter; nm | 8.97 (0.43) | 8.83 (0.34) | <0.001 |
Baseline fasting TG ≥ 150 mg/dL (N = 248) | |||
Small VLDL concentration, nmol/L | 43.62 (28.93) | 31.97 (18.10) | <0.001 |
Medium VLDL concentration, nmol/L | 74.12 (44.03) | 31.67 (28.32) | <0.001 |
Large VLDL concentration, nmol/L | 9.60 (11.74) | 4.55 (4.60) | <0.001 |
VLDL total particles; nmol/L | 127.38 (54.65) | 68.22 (37.96) | <0.001 |
VLDL diameter; nm | 52.84 (6.85) | 53.39 (7.35) | 0.09 |
Small LDL concentration, nmol/L | 1415.81 (539.35) | 1032.66 (445.66) | <0.001 |
Large LDL concentration, nmol/L | 247.00 (247.40) | 413.84 (232.50) | <0.001 |
LDL total particles; nmol/L | 1736.81 (488.611) | 1503.32 (404.81) | <0.001 |
LDL diameter; nm | 20.07 (0.72) | 20.67 (0.62) | <0.001 |
Small HDL concentration, nmol/L | 24.14 (5.54) | 24.03 (8.84) | 0.36 |
Medium HDL concentration, nmol/L | 2.23 (3.65) | 4.30 (5.08) | <0.001 |
Small VLDL concentration, nmol/L | 43.62 (28.93) | 31.97 (18.10) | <0.001 |
Medium VLDL concentration, nmol/L | 74.12 (44.03) | 31.67 (28.32) | <0.001 |
Large VLDL concentration, nmol/L | 9.60 (11.74) | 4.55 (4.60) | <0.001 |
NMR Measure | Min | Max | Mean (SD) | Genetic Risk Score | |||||
---|---|---|---|---|---|---|---|---|---|
GRS-Phenotype Associations | |||||||||
Baseline | Fenofibrate Response | ||||||||
F-Value | δ | p | F-Value | δ | p | ||||
Full GOLDN sample (n = 817) | |||||||||
Small VLDL concentration | 9.44 | 22.02 | 15.75 (2.11) | 0.04 | 0.01 | 0.85 | 0.45 | 0.05 | 0.50 |
Medium VLDL concentration | 5.26 | 13.65 | 9.79 (1.49) | 3.97 | 0.14 | 0.04 | 0.39 | 0.04 | 0.53 |
Large VLDL concentration | 9.16 | 22.49 | 15.87 (2.34) | 0.66 | 0.06 | 0.41 | 1.77 | 0.09 | 0.18 |
VLDL total particles | 1.01 | 8.34 | 5.15 (1.16) | 26.37 | 0.36 | <0.0001 * | 0.50 | 0.05 | 0.48 |
VLDL diameter | 1.00 | 10.09 | 5.32 (1.61) | 2.03 | 0.10 | <0.15 | 0.01 | 0.007 | 0.93 |
Small LDL concentration | 18.00 | 27.99 | 23.25 (1.63) | 8.90 | 0.21 | 0.003 * | 1.65 | 0.09 | 0.20 |
Large LDL concentration | 8.37 | 24.01 | 16.29 (2.48) | 11.48 | 0.24 | 0.0007 * | 0.00 | 0 | 0.99 |
LDL total particles | 5.96 | 19.65 | 12.39 (2.16) | 8.10 | 0.20 | 0.004 * | 0.24 | 0.03 | 0.62 |
LDL diameter | 0.14 | 7.97 | 3.55 (1.25) | 7.04 | 0.19 | 0.008 * | 0.24 | 0.03 | 0.63 |
Small HDL concentration | 5.00 | 18.01 | 10.64 (2.06) | 13.86 | 0.26 | 0.0002 * | 0.02 | 0.01 | 0.87 |
Medium HDL concentration | 7.27 | 17.27 | 12.25 (1.77) | 9.11 | 0.21 | 0.0003 * | 6.38 | 0.17 | 0.01 |
Large HDL concentration | 5.98 | 19.05 | 12.26 (1.97) | 12.14 | 0.24 | <0.0005 * | 0.19 | 0.03 | 0.67 |
HDL total particles | 1.19 | 10.88 | 5.91 (1.66) | 2.56 | 0.11 | 0.11 | 0.35 | 0.04 | 0.56 |
HDL diameter | 6.80 | 20.46 | 13.50 (2.23) | 10.05 | 0.22 | <0.002 * | 0.54 | 0.05 | 0.46 |
4. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Frazier-Wood, A.C.; Wojczynski, M.K.; Borecki, I.B.; Hopkins, P.N.; Lai, C.-Q.; Ordovas, J.M.; Straka, R.J.; Tsai, M.Y.; Tiwari, H.K.; Arnett, D.K. Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate. Biology 2014, 3, 536-550. https://doi.org/10.3390/biology3030536
Frazier-Wood AC, Wojczynski MK, Borecki IB, Hopkins PN, Lai C-Q, Ordovas JM, Straka RJ, Tsai MY, Tiwari HK, Arnett DK. Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate. Biology. 2014; 3(3):536-550. https://doi.org/10.3390/biology3030536
Chicago/Turabian StyleFrazier-Wood, Alexis C., Mary K. Wojczynski, Ingrid B. Borecki, Paul N. Hopkins, Chao-Qiang Lai, Jose M. Ordovas, Robert J. Straka, Micheal Y. Tsai, Hemant K. Tiwari, and Donna K. Arnett. 2014. "Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate" Biology 3, no. 3: 536-550. https://doi.org/10.3390/biology3030536