Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study - Sorbonne Université
Journal Articles Genes Year : 2020

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

Federica Laguzzi
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  • PersonId : 1095953
Fabrizio Veglia
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  • PersonId : 1093614
Lorenzo Vigo
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  • PersonId : 1106263
Elena Tremoli
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  • PersonId : 1093612
Ulf de Faire
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  • PersonId : 1106264
Per Eriksson
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  • PersonId : 1106265
Jiri Aubrecht
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  • PersonId : 1106266
Karin Leander
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  • PersonId : 1106267
Matteo Pirro
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  • PersonId : 1093615
Philippe Giral
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  • PersonId : 1106268
Anders Mälarstig
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  • PersonId : 1106269
Bruna Gigante
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  • PersonId : 1093609

Abstract

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.
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Dates and versions

hal-03298638 , version 1 (23-07-2021)

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Luigi Castaldo, Federica Laguzzi, Rona J Strawbridge, Damiano Baldassarre, Fabrizio Veglia, 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), pp.1243. ⟨10.3390/genes11111243⟩. ⟨hal-03298638⟩
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