PNPLA3 rs139051 is associated with phospholipid metabolite profile and hepatic inflammation in nonalcoholic fatty liver disease  

作　　者：Ji-Jun Luo Hai-Xia Cao Rui-Xu Yang Rui-Nan Zhang Qin Pan 

机构地区：[1]Department of Gastroenterology, Xinhua Hospital,Shanghai Jiaotong University School of Medicine

出　　处：《World Journal of Clinical Cases》2018年第10期355-364,共10页世界临床病例杂志

基　　金：Supported by National Key Research and Development Plan "Precision Medicine Research",No.2017YFC0908903;National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840;State Key Development Program for Basic Research of China,No.2012CB517501;100 Talents Program,No.XBR2011007h;Program of the Committee of Science and Technology,No.09140903500

摘　　要：AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease(NAFLD).METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms(SNPs) in PNPLA3. Ultra performance liquid chromatography-tandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs(rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine(LPC), lysophosphatidylcholine plasmalogen(LPCO), lysophosphatdylethanolamine(LPE), phosphatidylcholine(PC), choline plasmalogen(PCO), phosphatidylethanolamine(PE), ethanolamine plasmalogen(PEO)], of NAFLD patients. PNPLA3 rs139051(A/A genotype) and rs2294918(G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs(LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs(LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD(rho:-0.407 to-0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50(0.00, 1.75) vs 1.50(1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile.CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an upregulatory effect on serum phospholipids of AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease(NAFLD).METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms(SNPs) in PNPLA3. Ultra performance liquid chromatography-tandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs(rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine(LPC), lysophosphatidylcholine plasmalogen(LPCO), lysophosphatdylethanolamine(LPE), phosphatidylcholine(PC), choline plasmalogen(PCO), phosphatidylethanolamine(PE), ethanolamine plasmalogen(PEO)], of NAFLD patients. PNPLA3 rs139051(A/A genotype) and rs2294918(G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs(LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs(LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD(rho:-0.407 to-0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50(0.00, 1.75) vs 1.50(1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile.CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an upregulatory effect on serum phospholipids of

关 键 词：NONALCOHOLIC FATTY liver disease Patatin-like PHOSPHOLIPASE domain containing 3 Single NUCLEOTIDE POLYMORPHISM PHOSPHOLIPID Inflammation 

分 类 号：R[医药卫生]