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
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DOI：
10.1111/liv.14251
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发表时间：
2020-01-01
影响因子：
6.7
通讯作者：
Zheng, Ming-Hua
中科院分区：
文献类型：
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作者：
Sun, Dan-Qin;Zheng, Kenneth, I;Zheng, Ming-Hua
背景与目的Patatin-like phospholipase domain containing protein 3 (PNPLA3) rs738409多态性与NAFLD的严重程度相关，且PNPLA3基因在肾脏中表达，但PNPLA3 rs738409多态性是否也与肾小管损伤（RTI）相关尚不确定。我们评估了PNPLA3基因型对谷丙转氨酶水平正常（nALT）或异常（abnALT）的NAFLD患者RTI生物标志物和肾小球功能的影响。方法选取经组织学证实的NAFLD患者217例，其中持续nALT（低于正常上限3个月）75例。采用多变量回归分析来检验PNPLA3基因型与肾功能障碍生物标志物之间的相关性。结果与非alt组相比，nALT组患者尿中性粒细胞明胶酶相关脂钙蛋白水平（u-NGAL， RTI的生物标志物）较高（P < 0.001），尿白蛋白较高（P = 0.039），慢性肾病（CKD）患病率较高（P = 0.046）。在调整肾脏危险因素和NAFLD组织学严重程度后，pnpla3gg基因型与CKD和异常蛋白尿风险之间的相关性仍然显著，主要在nALT组。同样，pnpla3gg基因型与nALT组较高的u-NGAL水平相关，即使在调整了上述危险因素和肾小球滤过物标志物后也是如此（β系数：22.29,95% CI: 0.99-43.60, P = 0.041）。结论携带PNPLA3 rs738409 G等位基因的NAFLD合并持续性nALT患者早期肾小球和小管损伤的风险较高。我们认为PNPLA3基因分型可能有助于识别有较高RTI风险的NAFLD患者。
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 (beta-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.