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Article

Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study

1
Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80138 Naples, Italy
2
Department of Pharmacy, University of Naples “Federico II”, 80138 Naples, Italy
3
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
4
Mental Health and Wellbeing, Institute of Health and Wellbeing, University of Glasgow, Glasgow G12-8QQ, UK
5
Health Data Research University of Glasgow, College of Medicine, Veterinarian and Life Sciences, Glasgow G12-8RZ, UK
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Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden
7
Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Parea 4, 20138 Milan, Italy
8
Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milano MI, Italy
9
Department of Medicine, Division of vascular medicine University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
10
Takeda Pharmaceuticals International Co., Cambridge, 02139 MA, USA
11
Unit of Internal Medicine, Department of Medicine, University of Perugia, 06123 Perugia PG, Italy
12
Assistance Publique—Hopitaux de Paris; Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, 75013 Paris, France
*
Author to whom correspondence should be addressed.
Genes 2020, 11(11), 1243; https://doi.org/10.3390/genes11111243
Received: 3 October 2020 / Revised: 16 October 2020 / Accepted: 21 October 2020 / Published: 22 October 2020
(This article belongs to the Special Issue Cardiovascular Genetics)
Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development. View Full-Text
Keywords: carotid intima-media thickness; non-alcoholic fatty liver disease; alanine aminotransferase and genetic association study carotid intima-media thickness; non-alcoholic fatty liver disease; alanine aminotransferase and genetic association study
MDPI and ACS Style

Castaldo, L.; Laguzzi, F.; Strawbridge, R.J.; Baldassarre, D.; Veglia, F.; Vigo, L.; Tremoli, E.; de Faire, U.; Eriksson, P.; Smit, A.J.; Aubrecht, J.; Leander, K.; Pirro, M.; Giral, P.; Ritieni, A.; Di Minno, G.; Mälarstig, A.; Gigante, B., on behalf of IMPROVE Study Group 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://doi.org/10.3390/genes11111243

AMA Style

Castaldo L, Laguzzi F, Strawbridge RJ, Baldassarre D, Veglia F, Vigo L, Tremoli E, de Faire U, Eriksson P, Smit AJ, Aubrecht J, Leander K, Pirro M, Giral P, Ritieni A, Di Minno G, Mälarstig A, Gigante B on behalf of IMPROVE Study Group. 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://doi.org/10.3390/genes11111243

Chicago/Turabian Style

Castaldo, Luigi, Federica Laguzzi, Rona J. Strawbridge, Damiano Baldassarre, Fabrizio Veglia, Lorenzo Vigo, Elena Tremoli, Ulf de Faire, Per Eriksson, Andries J. Smit, Jiri Aubrecht, Karin Leander, Matteo Pirro, Philippe Giral, Alberto Ritieni, Giovanni Di Minno, Anders Mälarstig, and Bruna Gigante on behalf of IMPROVE Study Group. 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://doi.org/10.3390/genes11111243

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