Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Ethics
2.3. Ultrasonographic Measures
2.4. Genotyping
2.5. Statistical Analysis
3. Results
3.1. Clinical Characteristics
3.2. Association of rs738409 (C/G), rs10401969 (T/C), and rs1260326 (C/T) with c-IMT and ICCAD
3.3. Association of rs738409 (C/G), rs10401969 (T/C), and rs1260326 (C/T) with Metabolic Traits
3.4. Association of rs738409 (C/G), rs10401969 (T/C), and rs1260326 (C/T) with c-IMT and ICCAD after Stratification by ALT Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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rs738409 | rs10401969 | rs1260326 | |||||||
---|---|---|---|---|---|---|---|---|---|
n | CC | CG | GG | TT | CT + CC | CC | CT | TT | |
Men, n (%) | 3347 | 1070 (47.9) | 482 (48.9) | 46 (42.6) | 1385 (47.2) | 221(53.6) | 556 (52.0) | 712 (45.0) | 389 (53.4) |
Age, years | 3347 | 65.0 (59.8–67.3) | 64.2 (59.6–67.1) | 62.21 (58.6–66.6) | 64.3 (59.5–67.2) | 66.3 (60.8–67.2) | 64.6 (59.5–67.1) | 65.0 (60.1–67.4) | 63.8 (59.4–63.3) |
BMI, (kg/m2) | 3346 | 26.8 (24.2–29.3) | 26.9 (24.6–29.7) | 26.7 (24.1–30.9) | 26.8 (24.2–29.4) | 26.8 (24.6–29.8) | 27.28 (24.7–30.2) | 26.7 (24.2–29.1) | 24.5 (23.8–28.9) |
Cardiovascular Risk Factors, n (%) | |||||||||
Current smoke | 3347 | 351 (15.6) | 135 (13.7) | 16 (14.8) | 448 (15.6) | 54 (13.1) | 163 (15.2) | 223 (14.4) | 116 (15.9) |
Diabetes mellitus Type 2 | 3294 | 570 (25.7) | 267 (27.5) | 31 (29.8) | 751 (26.0) | 117 (28.7) | 333 (31.7) | 382 (25.11) | 153 (21.2) |
Hypertension | 3347 | 1787 (79.28) | 789 (80.1) | 85 (78.7) | 2310 (78.7) | 351 (85.2) | 881 (82.3) | 1218 (78.63) | 562 (77.2) |
Biochemical Measurements | |||||||||
TC | 3341 | 5.4 (4.7–6.2) | 5.4 (4.7–6.2) | 5.6 (4.5–6.4) | 5.5 (4.7–6.2) | 5.2 (4.6–6.0) | 5.3 (4.6–6.2) | 5.4 (4.7–6.2) | 5.6 (4.9–6.3) |
LDL-C | 3347 | 3.5 (2.8–4.2) | 3.5 (2.8–4.2) | 3.6 (2.7–4.5) | 3.5 (2.8–4.2) | 3.4 (2.9–4.1) | 3.5 (2.8–4.2) | 3.5 (2.8–4.2) | 3.64 (3.0–4.3) |
HDL-C | 3341 | 1.2 (1.0–1.5) | 1.2 (1.0–1.4) | 1.2 (1.0–1.4) | 1.2 (1.0–1.5) | 1.2 (1.0–1.4) | 1.2 (1.0–1.5) | 1.2 (1.0–1.5) | 1.2 (1.0–1.5) |
TG | 3341 | 1.3 (0.9–1.9) | 1.3 (0.9–1.9) | 1.3 (0.9–1.7) | 1.3 (0.9–1.9) | 1.2 (0.9–1.7) | 1.2 (0.9–1.7) | 1.3 (0.9–1.8) | 1.4 (1.0–2.1) |
Glucose | 3341 | 5.5 (4.9–6.3) | 5.5 (5.0–6.4) | 5.4 (4.9–6.4) | 5.5 (4.9–6.3) | 5.6 (5.1–6.6) | 5.6 (5.1–6.5) | 5.5 (5.0–6.3) | 5.4 (4.8–6.0) |
ALT | 3347 | 20 (16.0–27.0) | 21 (17.0–29.0) | 23.5 (17.5–34.5) | 20 (16–27) | 22 (17.0–30.0) | 21 (17.0–29.0) | 20 (16.0–27.0) | 20 (17.0–27.0) |
Ultrasonographic Measures (mm) | |||||||||
C-IMTmean | 3346 | 0.85 (0.7–1.0) | 0.85 (0.7–1.0) | 0.81 (0.7–0.9) | 0.85 (0.7–1.0) | 0.87 (0.8–1.0) | 0.86 (0.7–1.0) | 0.85 (0.7–1.0) | 0.84 (0.7–1.0) |
C-IMTmax | 3346 | 1.85 (1.4–2.5) | 1.93 (1.4–2.6) | 1.84 (1.4–2.3) | 1.85 (1.4–2.5) | 1.93 (1.4–2.5) | 1.93 (1.4–2.6) | 1.85 (1.4–2.5) | 1.84 (1.4–2.4) |
C-IMTmean-max | 3347 | 1.19 (1.0–1.4) | 1.20 (1.0–1.4) | 1.13 (1.0–1.3) | 1.18 (1.0–1.4) | 1.23 (1.1–1.4) | 1.22 (1.0–1.4) | 1.19 (1.0–1.4) | 1.17 (1.0–1.4) |
ICCAD | 3347 | 7.72 (7.2–8.3) | 7.82 (7.2–8.4) | 7.55 (7.1–8.0) | 7.73 (7.2–8.3) | 7.82 (7.2–8.4) | 7.85 (7.3–8.4) | 7.71 (7.2–8.3) | 7.64 (7.2–8.2) |
Ultrasonographic Measures | n | SNP | EA | Model 1 | Model 2 | ||||
---|---|---|---|---|---|---|---|---|---|
β | SE | p | β | SE | p | ||||
c-IMTmean | 3346 | rs738409 | G | −0.002 | 0.0029 | 0.443 | −0.001 | 0.003 | 0.818 |
rs10401969 | C | 0.012 | 0.005 | 0.025 | 0.001 | 0.004 | 0.768 | ||
rs1260326 | T | −0.004 | 0.002 | 0.060 | 0.003 | 0.002 | 0.179 | ||
c-IMTmax | 3346 | rs738409 | G | 0 | 0.006 | 0.963 | 0.002 | 0.005 | 0.636 |
rs10401969 | C | 0.014 | 0.009 | 0.108 | 0 | 0.008 | 0.970 | ||
rs1260326 | T | −0.01 | 0.004 | 0.013 | 0.001 | 0.004 | 0.810 | ||
c-IMTmean-max | 3347 | rs738409 | G | −0.003 | 0.003 | 0.353 | −0.001 | 0.003 | 0.663 |
rs10401969 | C | 0.014 | 0.005 | 0.006 | 0.003 | 0.005 | 0.476 | ||
rs1260326 | T | −0.005 | 0.002 | 0.02 | 0.003 | 0.002 | 0.176 | ||
ICCAD | 3347 | rs738409 | G | 0 | 0.001 | 0.499 | 0.002 | 0.001 | 0.174 |
rs10401969 | C | 0.006 | 0.002 | 0.015 | 0.001 | 0.002 | 0.732 | ||
rs1260326 | T | −0.005 | 0.001 | <0.001 | −0.001 | −0.001 | 0.271 |
Metabolic Traits | n | SNP | EA | Model 1 | Model 2 | ||||
---|---|---|---|---|---|---|---|---|---|
β | SE | p | β | SE | p | ||||
ALT | 3347 | rs738409 | G | 0.031 | 0.006 | <0.001 | 0.029 | 0.006 | <0.001 |
rs10401969 | C | 0.042 | 0.01 | <0.001 | 0.040 | 0.009 | <0.001 | ||
rs1260326 | T | −0.012 | 0.004 | 0.009 | −0.008 | 0.004 | 0.062 | ||
BMI | 3346 | rs738409 | G | 0.296 | 0.136 | 0.029 | 0.265 | 0.132 | 0.045 |
rs10401969 | C | 0.181 | 0.225 | 0.421 | −0.038 | 0.219 | 0.816 | ||
rs1260326 | T | −0.569 | 0.101 | <0.001 | −0.224 | 0.102 | 0.028 | ||
TC | 3341 | rs738409 | G | −0.025 | 0.036 | 0.489 | −0.026 | 0.034 | 0.441 |
rs10401969 | C | −0.13 | 0.059 | 0.028 | −0.042 | 0.057 | 0.465 | ||
rs1260326 | T | 0.122 | 0.027 | <0.001 | 0.027 | 0.027 | 0.312 | ||
LDL-C | 3347 | rs738409 | G | −0.008 | 0.032 | 0.803 | −0.007 | 0.031 | 0.831 |
rs10401969 | C | −0.096 | 0.053 | 0.069 | −0.022 | 0.051 | 0.659 | ||
rs1260326 | T | 0.064 | 0.024 | 0.008 | −0.027 | 0.024 | 0.255 | ||
TG | 3341 | rs738409 | G | −0.018 | 0.026 | 0.474 | −0.022 | 0.025 | 0.388 |
rs10401969 | C | −0.044 | 0.042 | 0.300 | −0.030 | 0.042 | 0.482 | ||
rs1260326 | T | 0.114 | 0.019 | <0.001 | 0.105 | 0.020 | <0.001 | ||
Glucose | 2426 | rs738409 | G | 0.024 | 0.025 | 0.344 | 0.027 | 0.023 | 0.233 |
rs10401969 | C | 0.087 | 0.041 | 0.035 | 0.033 | 0.038 | 0.376 | ||
rs1260326 | T | −0.087 | 0.018 | <0.001 | −0.031 | 0.017 | 0.076 |
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Castaldo, L.; Laguzzi, F.; Strawbridge, R.J.; Baldassarre, D.; Veglia, F.; Vigo, L.; Tremoli, E.; de Faire, U.; Eriksson, P.; Smit, A.J.; et al. Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study. Genes 2020, 11, 1243. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111243
Castaldo L, Laguzzi F, Strawbridge RJ, Baldassarre D, Veglia F, Vigo L, Tremoli E, de Faire U, Eriksson P, Smit AJ, et al. Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study. Genes. 2020; 11(11):1243. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111243
Chicago/Turabian StyleCastaldo, Luigi, Federica Laguzzi, Rona J. Strawbridge, Damiano Baldassarre, Fabrizio Veglia, Lorenzo Vigo, Elena Tremoli, Ulf de Faire, Per Eriksson, Andries J. Smit, and et al. 2020. "Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study" Genes 11, no. 11: 1243. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111243