Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2020; 26(36): 5474-5483
Published online Sep 28, 2020. doi: 10.3748/wjg.v26.i36.5474
Pediatric non-alcoholic fatty liver disease and kidney function: Effect of HSD17B13 variant
Anna Di Sessa, Giuseppina Rosaria Umano, Grazia Cirillo, Antonio Paride Passaro, Valentina Verde, Domenico Cozzolino, Stefano Guarino, Pierluigi Marzuillo, Emanuele Miraglia del Giudice
Anna Di Sessa, Giuseppina Rosaria Umano, Grazia Cirillo, Antonio Paride Passaro, Valentina Verde, Stefano Guarino, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
Domenico Cozzolino, Department of Internal Medicine, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
Author contributions: Di Sessa A and Miraglia del Giudice E contributed to the research idea and study design; Guarino S, Umano GR, Passaro AP, and Verde V contributed to data acquisition; Cirillo G and Umano GR contributed to the molecular analysis; Marzuillo P, Miraglia del Giudice E and Cozzolino D contributed to the data analysis/interpretation; Di Sessa A and Marzuillo P contributed to statistical analysis; Miraglia del Giudice E and Marzuillo P contributed to supervision or mentorship. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Institutional review board statement: The study was approved by the Institutional Review Board of Università degli Studi della Campania Luigi Vanvitelli.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: Nothing to declare.
Data sharing statement: Datasets generated during analyses are available on request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Pierluigi Marzuillo, MD, PhD, Doctor, Postdoc, Postdoctoral Fellow, Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Via Luigi De Crecchio 2, Napoli 80138, Italy. pierluigi.marzuillo@gmail.com
Received: April 1, 2020
Peer-review started: April 1, 2020
First decision: May 29, 2020
Revised: June 2, 2020
Accepted: September 4, 2020
Article in press: September 4, 2020
Published online: September 28, 2020
Abstract
BACKGROUND

Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3 (PNPLA3) and the E167K allele in the transmembrane 6 superfamily member 2 gene (TM6SF2) affect renal function. Recently the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children.

AIM

To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children.

METHODS

We enrolled 684 obese children (mean age 10.56 ± 2.94 years; mean BMI-SDS 2.98 ± 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made.

RESULTS

Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD. Homozygous patients for HSD17B13 genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele (P value for intercepts = 0.005; P value for slopes = 0.94). The same effect was observed among patients without NAFLD (P value for intercepts = 0.0012; P value for slopes = 0.87).

CONCLUSION

Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.

Keywords: Hydroxysteroid, Dehydrogenase, Fatty, Liver, Renal, Function, Obese, Children

Core Tip: Compelling evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease. In particular, both the major NAFLD risk polymorphisms such as the I148M polymorphism in the PNPLA3 and the E167K allele in the TM6SF2 gene affect renal function. Recently the rs72613567 variant in the HSD17B13 gene has been recognized as a novel genetic protective variant in the NAFLD scenario. We aimed to evaluate the effect of this variant on renal function in obese children.