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
Genes 11 (11) 1243 [2020-10-22; online 2020-10-22]
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.