Published online Sep 28, 2020. doi: 10.3748/wjg.v26.i36.5474
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
Accumulating data supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), mostly sustained by 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). Recently the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology with a protective role against liver damage both in adults and children.
Despite a growing interest regarding the potential genetic link between NAFLD and CKD, available literature data showed no studies investigating the effect of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children.
In this study we aimed to evaluate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children.
Anthropometric, laboratory, and instrumental evaluations were conducted in all the enrolled 684 obese children. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also performed.
Patients carrying the HSD17B13 rare A allele had higher eGFR levels than homozygous patients both among subjects with and without NAFLD. This association was independent of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. The eGFR decline in homozygous subjects for HSD17B13 genotype with and without NAFLD was more markedly with the increase of the age than in carriers the HSD17B13 rare A allele.
In line with the beneficial effect against NAFLD risk, the rs72613567:TA variant of the HSD17B13 gene exerts a protective role also on renal function in obese children with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.
Findings from this study highlight the importance of a better NAFLD genetic assessment as possible clinical tool for improved strategies to identify patients at higher cardiometabolic risk already in childhood.