PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels
PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels
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.
chronic kidney disease, non-alcoholic fatty liver disease, patatin-like phospholipase domain-containing protein 3, renal tubular injury
107-119
Sun, Dan-Qin
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Zheng, Kenneth I.
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Xu, Gang
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Ma, Hong-Lei
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Zhang, Hao-Yang
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Pan, Xiao-Yan
8ab20b3c-df10-4275-9845-102c2153994f
Zhu, Pei-Wu
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Wang, Xiao-Dong
d1343a29-1dab-4dff-ab04-64eaa1c5b559
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Chen, Yong-Ping
84e76c57-d092-4672-9cf5-2a58abec941e
Yuan, Wei-Jie
635cef68-e718-4d02-ba8f-d4e333ca0101
Zheng, Ming-Hua
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1 January 2020
Sun, Dan-Qin
e1ab05b2-a9f4-4d00-be57-128e5a5c9e4d
Zheng, Kenneth I.
99a75ea6-19db-4110-8871-d21d5b545058
Xu, Gang
7c42f7d2-67fb-4c7e-92c9-63281a339c65
Ma, Hong-Lei
3e3ee59c-fe7c-45cd-9d63-1dfab2857974
Zhang, Hao-Yang
5669cc7c-58c6-4017-97eb-ccf657e2cb9a
Pan, Xiao-Yan
8ab20b3c-df10-4275-9845-102c2153994f
Zhu, Pei-Wu
6faa8825-1866-4edd-87f2-e497bf702d04
Wang, Xiao-Dong
d1343a29-1dab-4dff-ab04-64eaa1c5b559
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Chen, Yong-Ping
84e76c57-d092-4672-9cf5-2a58abec941e
Yuan, Wei-Jie
635cef68-e718-4d02-ba8f-d4e333ca0101
Zheng, Ming-Hua
56c24dc2-bb08-47b1-8736-b41fcad338e4
Sun, Dan-Qin, Zheng, Kenneth I., Xu, Gang, Ma, Hong-Lei, Zhang, Hao-Yang, Pan, Xiao-Yan, Zhu, Pei-Wu, Wang, Xiao-Dong, Targher, Giovanni, Byrne, Christopher, Chen, Yong-Ping, Yuan, Wei-Jie and Zheng, Ming-Hua
(2020)
PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels.
Liver International, 40 (1), .
(doi:10.1111/liv.14251).
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 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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Accepted/In Press date: 9 September 2019
e-pub ahead of print date: 13 September 2019
Published date: 1 January 2020
Additional Information:
Funding Information:
Funding information This work was supported by grants from the National Natural Science Foundation of China (81500665), High Level Creative Talents from Department of Public Health in Zhejiang Province, Project of New Century 551 Talent Nurturing in Wenzhou and General Program of Science and Technology Development Foundation of Nanjing Medical University (2017NJMU168). GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. We thank Prof Ji-Min Liu, a pathologist from McMaster University, who conducted quality control of liver pathology data in the Wenzhou cohort. This work is a part of the PERSONS study.
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Keywords:
chronic kidney disease, non-alcoholic fatty liver disease, patatin-like phospholipase domain-containing protein 3, renal tubular injury
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Local EPrints ID: 434045
URI: http://eprints.soton.ac.uk/id/eprint/434045
ISSN: 1478-3223
PURE UUID: 45538259-6434-4746-b167-710dd9711f36
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Date deposited: 11 Sep 2019 16:30
Last modified: 17 Mar 2024 02:49
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Contributors
Author:
Dan-Qin Sun
Author:
Kenneth I. Zheng
Author:
Gang Xu
Author:
Hong-Lei Ma
Author:
Hao-Yang Zhang
Author:
Xiao-Yan Pan
Author:
Pei-Wu Zhu
Author:
Xiao-Dong Wang
Author:
Giovanni Targher
Author:
Yong-Ping Chen
Author:
Wei-Jie Yuan
Author:
Ming-Hua Zheng
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