Dan-Qin Sun1,2, Kenneth I Zheng3, Gang Xu4, Hong-Lei Ma3, Hao-Yang Zhang5, Xiao-Yan Pan6, Pei-Wu Zhu4, Xiao-Dong Wang3,7, Giovanni Targher8, Christopher D Byrne9, Yong-Ping Chen3,7, Wei-Jie Yuan2, Ming-Hua Zheng3,7. 1. Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China. 2. Department of Nephrology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China. 3. NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 4. Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 5. School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China. 6. Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 7. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China. 8. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. 9. Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK.
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.
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 PNPLA3rs738409 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 PNPLA3rs738409 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.
Authors: Ke Xu; Kenneth I Zheng; Pei-Wu Zhu; Wen-Yue Liu; Hong-Lei Ma; Gang Li; Liang-Jie Tang; Rafael S Rios; Giovanni Targher; Christopher D Byrne; Xiao-Dong Wang; Yong-Ping Chen; Ming-Hua Zheng Journal: J Clin Transl Hepatol Date: 2021-07-29