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. 2022 Mar 19;10(3):720.
doi: 10.3390/biomedicines10030720.

Metabolic Syndrome but Not Fatty Liver-Associated Genetic Variants Correlates with Glomerular Renal Function Decline in Patients with Non-Alcoholic Fatty Liver Disease

Francesco Baratta  1 , Laura D'Erasmo  2 , Alessia Di Costanzo  2 , Ilaria Umbro  1 , Daniele Pastori  1 , Francesco Angelico  3 , Maria Del Ben  1
Affiliations

Metabolic Syndrome but Not Fatty Liver-Associated Genetic Variants Correlates with Glomerular Renal Function Decline in Patients with Non-Alcoholic Fatty Liver Disease

Francesco Baratta et al. Biomedicines. .

Abstract

The association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has been extensively demonstrated. Recent studies have focused attention on the role of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism in the association between NAFLD and CKD in non-metabolic adults and children, but the genetic impact on NAFLD-CKD association is still a matter of debate. The aim of the study was to investigate the impact of PNPLA3, transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and glucokinase regulatory protein (GCKR) gene variants rather than metabolic syndrome features on renal function in a large population of NAFLD patients. The present study is a post hoc analysis of the Plinio Study (ClinicalTrials.gov: NCT04036357). PNPLA3, TM6SF2, MBOAT7 and GCKR genes were analyzed by using real-time PCR with TaqMan probes. Glomerular filtration rate (GFR) was estimated with CKD-EPI. We analyzed 538 NAFLD; 47.2% had GFR < 90 mL/min/1.73 m2 while 5.9% had GFR < 60 mL/min/1.73 m2. The distribution of genotypes was superimposable according to GFR cut-offs. Results from the multivariable regression model did not show any correlation between genotypes and renal function. Conversely, metabolic syndrome was highly associated with GFR < 90 mL/min/1.73 m2 (odds ratio (OR): 1.58 [1.10−2.28]) and arterial hypertension with GFR < 60 mL/min/1.73 m2 (OR: 1.50 [1.05−2.14]). In conclusion, the association between NAFLD and CKD might be related to the shared metabolic risk factors rather than the genetic NAFLD background.

Keywords: GCKR; MBOAT7; PNPLA3; TM6SF2; chronic kidney disease; glomerular filtration rate; kidney; non-alcoholic fatty liver disease; renal function.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Box plots of eGFR according to PNPLA3 (Panel A), MBOAT7 (Panel B), TM6SF2 (Panel C) and GCKR (Panel D) genotypes.
See this image and copyright information in PMC

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