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PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients
  • ISSN号:1007-9327
  • 期刊名称:《世界胃肠病学杂志:英文版》
  • 时间:0
  • 分类:R657.3[医药卫生—临床医学;医药卫生—外科学]
  • 作者机构:Key Laboratory of Combined Multi-Organ Transplantation,Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,First Affiliated Hospital,School of Medicine,Zhejiang University
  • 相关基金:Supported by National S and T Major Project,No.2012ZX 10002017;Foundation for Innovative Research Groups of the National Natural Science Foundation of China,Grant No.81421062;China Postdoctoral Science Foundation Project,No.2015M570518
中文摘要:

De novo non-alcoholic fatty liver disease(NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148 M and TM6SF2 E167 K polymorphisms affected NAFLD susceptibility in the general population. However,this association was not validated in survivors after liver transplantation(LT). We performed a crosssectional survey to investigate this relationship. A comprehensive survey,including anthropometric measurements,fasting venous blood sampling,ultrasound,and questionnaires was performed in the shortterm. The clinical indications and patient’s steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers(0.33 vs 0.10 for GG vs CC + CG carriers,P = 0.018),while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism(0.19 in CC vs 0.14 in CT + TT carriers,P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novoNAFLD following a recessive model(GG vs CC + CG,OR = 14.2,95%CI:1.78-113,P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity(defined as body mass index > 25 kg/m2),steatosis was highly prevalent(71.4%) in PNPLA3 GG carriers Table 1 Current status of long-term recipients surviving more than 10 years Univariate Multivariate NAFLD(n = 12)Control(n = 53)P value OR P value Age(yr) 56.5 ± 8.4 53.6 ± 10.1 0.356 1.04(0.92-1.18)0.528Gender(M/F) 10/2 47/6 0.611 1.40(0.14-14.2)0.427 Indication for LT Hepatitis/cirrhosis/ cancer/others1/8/2/17/35/9/20.889 Survival time(yr) 11.2 ± 0.9 11.5 ± 1.4 0.541 BMI(kg/m2) 25.1 ± 3.0 22.5 ± 2.6 0.003 1.47(1.03-2.08)0.032 TG(mmol/L) 1.6 ± 1.1 1.1 ± 0.6 0.038 1.34(0.38-4.71)0.652 HDL-C(mmol/L) 1.2(1.0-1.4) 1.3(1.0-1.7) 0.267 FBG(mmol/L) 7.6 ± 3.4 5.7 ± 1.9 0.013 1.49(0.93-2.37)0.095 Hypertension(Yes/no)3/9 21/32 0.343

英文摘要:

De novo non-alcoholic fatty liver disease(NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148 M and TM6SF2 E167 K polymorphisms affected NAFLD susceptibility in the general population. However,this association was not validated in survivors after liver transplantation(LT). We performed a crosssectional survey to investigate this relationship. A comprehensive survey,including anthropometric measurements,fasting venous blood sampling,ultrasound,and questionnaires was performed in the shortterm. The clinical indications and patient’s steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers(0.33 vs 0.10 for GG vs CC + CG carriers,P = 0.018),while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism(0.19 in CC vs 0.14 in CT + TT carriers,P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novoNAFLD following a recessive model(GG vs CC + CG,OR = 14.2,95%CI:1.78-113,P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity(defined as body mass index > 25 kg/m2),steatosis was highly prevalent(71.4%) in PNPLA3 GG carriers Table 1 Current status of long-term recipients surviving more than 10 years Univariate Multivariate NAFLD(n = 12)Control(n = 53)P value OR P value Age(yr) 56.5 ± 8.4 53.6 ± 10.1 0.356 1.04(0.92-1.18)0.528Gender(M/F) 10/2 47/6 0.611 1.40(0.14-14.2)0.427 Indication for LT Hepatitis/cirrhosis/ cancer/others1/8/2/17/35/9/20.889 Survival time(yr) 11.2 ± 0.9 11.5 ± 1.4 0.541 BMI(kg/m2) 25.1 ± 3.0 22.5 ± 2.6 0.003 1.47(1.03-2.08)0.032 TG(mmol/L) 1.6 ± 1.1 1.1 ± 0.6 0.038 1.34(0.38-4.71)0.652 HDL-C(mmol/L) 1.2(1.0-1.4) 1.3(1.0-1.7) 0.267 FBG(mmol/L) 7.6 ± 3.4 5.7 ± 1.9 0.013 1.49(0.93-2.37)0.095 Hypertension(Yes/no)3/9 21/32 0.343

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  • 《世界胃肠病学杂志:英文版》
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  • 国际标准刊号:ISSN:1007-9327
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