Genetic variants associated with non-alcoholic fatty liver disease do not associate with measures of sub-clinical atherosclerosis: results from the IMPROVE study

Castaldo, L. 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(11), 1243. (doi: 10.3390/genes11111243) (PMID:33105679) (PMCID:PMC7690395)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Creator Roles:
Strawbridge, R. J.Writing – original draft
Authors: 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., and Gigante, B.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Genes
Publisher:MDPI
ISSN:2073-4425
ISSN (Online):2073-4425
Published Online:22 October 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Genes 11(11): 1243
Publisher Policy:Reproduced under a Creative Commons License

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