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PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels

Sun, Dan Qin ; Zheng, Kenneth I. ; Xu, Gang ; Ma, Hong Lei ; Zhang, Hao Yang LU orcid ; Pan, Xiao Yan ; Zhu, Pei Wu ; Wang, Xiao Dong ; Targher, Giovanni and Byrne, Christopher D. , et al. (2020) In Liver International 40(1). p.107-119
Abstract

Background & Aims: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. Methods: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between... (More)

Background & Aims: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. Methods: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. Results: The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P <.001), higher albuminuria (P =.039) and greater prevalence of chronic kidney disease (CKD; P =.046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (β-coefficient: 22.29, 95% CI: 0.99-43.60, P =.041). Conclusion: Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.

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publishing date
type
Contribution to journal
publication status
published
keywords
chronic kidney disease, non-alcoholic fatty liver disease, patatin-like phospholipase domain-containing protein 3, renal tubular injury
in
Liver International
volume
40
issue
1
pages
107 - 119
publisher
Wiley-Blackwell
external identifiers
  • pmid:31519069
  • scopus:85073932665
ISSN
1478-3223
DOI
10.1111/liv.14251
language
English
LU publication?
no
additional info
Publisher Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
id
ff7792d8-b57d-4e41-9a31-c2c79bc66e3d
date added to LUP
2024-02-05 15:58:40
date last changed
2024-07-02 21:44:00
@article{ff7792d8-b57d-4e41-9a31-c2c79bc66e3d,
  abstract     = {{<p>Background &amp; Aims: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. Methods: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. Results: The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P &lt;.001), higher albuminuria (P =.039) and greater prevalence of chronic kidney disease (CKD; P =.046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (β-coefficient: 22.29, 95% CI: 0.99-43.60, P =.041). Conclusion: Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.</p>}},
  author       = {{Sun, Dan Qin and Zheng, Kenneth I. and Xu, Gang and Ma, Hong Lei and Zhang, Hao Yang and Pan, Xiao Yan and Zhu, Pei Wu and Wang, Xiao Dong and Targher, Giovanni and Byrne, Christopher D. and Chen, Yong Ping and Yuan, Wei Jie and Zheng, Ming Hua}},
  issn         = {{1478-3223}},
  keywords     = {{chronic kidney disease; non-alcoholic fatty liver disease; patatin-like phospholipase domain-containing protein 3; renal tubular injury}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{107--119}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Liver International}},
  title        = {{PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels}},
  url          = {{http://dx.doi.org/10.1111/liv.14251}},
  doi          = {{10.1111/liv.14251}},
  volume       = {{40}},
  year         = {{2020}},
}