过氧化物酶体增殖激活物受体γ辅激活因子1α rs8192678位点单核苷酸多态性与非酒精性脂肪性肝病发病风险的关系
DOI: 10.3969/j.issn.1001-5256.2020.09.025
Association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha rs8192678 single nucleotide polymorphism with the risk of nonalcoholic fatty liver disease
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摘要:
目的探讨过氧化物酶体增殖激活物受体γ辅激活因子1α(PPARGC1A) rs8192678单核苷酸多态性(SNP)与非酒精性脂肪性肝病(NAFLD)发病风险的关系以及该位点SNP对相关生化指标的影响。方法选取2017年12月-2018年12月在青岛市市立医院就诊的NAFLD患者119例,并选取同期健康体检者213作为对照。采集所有受试者的临床数据和血液样本,检测血液样本的生化指标和PPARGC1A rs8192678位点SNP。采用χ2检验判断样本的基因型分布是否符合Hardy-Weinberg平衡法则。计量资料两组间比较采用t检验或Wilcoxon秩和检验。计数资料两组间比较采用χ2检验。采用二元logistic回归分析NAFLD发生的危险因素。结果 NAFLD组和对照组PPARGC1A rs8192678位点的基因型与等位基因分布差异均无统计学意义(χ2值分别为0.011、0.015,P值分别为0.918、0.904)。二元logistic回归分析显示,PPARGC1A rs8192678位点CT基因型不是NAFLD发生的危险因素(比值比=0.951,95%可信区间:0.368~2...
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关键词:
- 非酒精性脂肪性肝病 /
- 过氧化物酶体增殖物激活受体γ共激活因子1α /
- 多态性,单核苷酸
Abstract:Objective To investigate the association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha( PPARGC1 A) rs8192678 single nucleotide polymorphism( SNP) with the risk of nonalcoholic fatty liver disease( NAFLD) and the influence of PPARGC1 A rs8192678 SNP on NAFLD-related biochemical parameters. Methods A total of 119 NAFLD patients who attended Qingdao Municipal Hospital Affiliated to Qingdao University from December 2017 to December 2018 were enrolled as NAFLD group,and 213 individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical data and blood samples were collected from all subjects to measure related biochemical parameters and detect PPARGC1 A rs8192678 SNP. The chi-square test was used to determine whether the genotype distribution of samples was in accordance with the Hardy-Weinberg equilibrium. The t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups. A binary logistic regression analysis was used to investigate the risk factors for NAFLD.Results There were no significant differences in the genotype and allele frequencies of PPARGC1 A rs8192678 between the NAFLD group and the control group( χ2= 0. 011 and 0. 015,P = 0. 918 and 0. 904). The binary logistic regression analysis showed that CT genotype of PPARGC1 A rs8192678 was not a risk factor for NAFLD( odds ratio = 0. 951,95% confidence interval: 0. 368-2. 457,P = 0. 918). In the NAFLD group,the patients carrying CT genotype had a significantly higher level of gamma-glutamyl transpeptidase( GGT) than those carrying CC genotype( Z =-2. 331,P = 0. 020). Conclusion PPARGC1 A rs8192678 SNP does not increase the risk of NAFLD,while NAFLD patients carrying CT genotype tend to have a higher serum level of GGT.
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[1] YKI-JRVINEN H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome[J]. Lancet Diabetes Endocrinol,2014,2(11):901-910. [2] LI J,ZOU B,YEO YH,et al. Prevalence,incidence,and outcome of non-alcoholic fatty liver disease in Asia,1999-2019:A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol,2019,4(5):389-398. [3] PAIS R,BARRITT AS 4th,CALMUS Y,et al. NAFLD and liver transplantation:Current burden and expected challenges[J].J Hepatol,2016,65(6):1245-1257. [4] YOUNOSSI ZM,KOENIG AB,ABDELATIF D,et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J]. Hepatology,2016,64(1):73-84. [5] ZHOU F,ZHOU J,WANG W,et al. Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018:A systematic review and Meta-analysis[J]. Hepatology,2019,70(4):1119-1133. [6] FAN JG,KIM SU,WONG VW. New trends on obesity and NAFLD in Asia[J]. J Hepatol,2017,67(4):862-873. [7] CHANG Y,JUNG HS,CHO J,et al. Metabolically healthy obesity and the development of nonalcoholic fatty liver disease[J]. Am J Gastroenterol,2016,111(8):1133-1140. [8] KOO BK,KIM D,JOO SK,et al. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis[J]. J Hepatol,2017,66(1):123-131. [9] WONG VW,WONG GL,TSE CH,et al. Prevalence of the TM6SF2variant and non-alcoholic fatty liver disease in Chinese[J]. J Hepatol,2014,61(3):708-709. [10] LI Y,XU C,YU C,et al. Association of serum uric acid level with non-alcoholic fatty liver disease:A cross-sectional study[J]. J Hepatol,2009,50(5):1029-1034. [11] CUSI K,SANYAL AJ,ZHANG S,et al. Non-alcoholic fatty liver disease(NAFLD)prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes[J].Diabetes Obes Metab,2017,19(11):1630-1634. [12] TARGHER G,BYRNE CD,LONARDO A,et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease:A meta-analysis[J]. J Hepatol,2016,65(3):589-600. [13] ESLAM M,VALENTI L,ROMEO S. Genetics and epigenetics of NAFLD and NASH:Clinical impact[J]. J Hepatol,2018,68(2):268-279. [14] WU Z,BOSS O. Targeting PGC-1 alpha to control energy homeostasis[J]. Expert Opin Ther Targets,2007,11(10):1329-1338. [15] FANELLI M,FILIPPI E,SENTINELLI F,et al. The Gly482Ser missense mutation of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1 alpha)gene associates with reduced insulin sensitivity in normal and glucose-intolerant obese subjects[J]. Dis Markers,2005,21(4):175-180. [16] DU Q,TAN Z,SHI F,et al. PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation[J]. Cancer Sci,2019,110(6):2050-2062. [17] YANG S,HWANG S,JANG J,et al. PGC1αis required for the induction of contact inhibition by suppressing ROS[J].Biochem Biophys Res Commun,2018,501(3):739-744. [18] QIAN J,CHEN S,HUANG Y,et al. PGC-1αregulates hepatic hepcidin expression and iron homeostasis in response to inflammation[J]. Mol Endocrinol,2013,27(4):683-692. [19] YONEDA M,HOTTA K,NOZAKI Y,et al. Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease(NAFLD)[J]. BMC Gastroenterol,2008,8:27. [20] MORADI S,MIRZAEI K,MAGHBOOLI Z,et al. Variants in the PPARGC1A gene may influence the effect of fat intake on resting metabolic rate in obese women[J]. Lipids,2018,53(3):291-300. [21] Group of Fatty Liver and Alcoholic Liver Diseases,Society of Hepatology,Chinese Medical Association. Guidelines for Management of non-alcoholic fatty liver disease[J]. J Clin Hepatol,2010,26(2):120-124.(in Chinese)中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].临床肝胆病杂志,2010,26(2):120-124. [22] PICCININ E,VILLANI G,MOSCHETTA A. Metabolic aspects in NAFLD,NASH and hepatocellular carcinoma:The role of PGC1 coactivators[J]. Nat Rev Gastroenterol Hepatol,2019,16(3):160-174. [23] NITZ I,EWERT A,KLAPPER M,et al. Analysis of PGC-1alpha variants Gly482Ser and Thr612Met concerning their PPARgamma2-coactivation function[J]. Biochem Biophys Res Commun,2007,353(2):481-486. [24] BESSE-PATIN A,LéVEILLéM,OROPEZA D,et al. Estrogen signals through peroxisome proliferator-activated receptor-γcoactivator 1αto reduce oxidative damage associated with diet-induced fatty liver disease[J]. Gastroenterology,2017,152(1):243-256. [25] CHEN Y,MU P,HE S,et al. Gly482Ser mutation impairs the effects of peroxisome proliferator-activated receptorγcoactivator-1αon decreasing fat deposition and stimulating phosphoenolpyruvate carboxykinase expression in hepatocytes[J]. Nutr Res,2013,33(4):332-339. [26] KOZAKOVA M,PALOMBO C,ENG MP,et al. Fatty liver index,gamma-glutamyltransferase,and early carotid plaques[J]. Hepatology,2012,55(5):1406-1415. [27] XU Y,BI YF,XU M,et al. Cross-sectional and longitudinal association of serum alanine aminotransaminase andγ-glutamyltransferase with metabolic syndrome in middle-aged and elderly Chinese people[J]. J Diabetes,2011,3(1):38-47. [28] BOTTON J,HEUDE B,ANDRE P,et al. Relationship between gamma-glutamyltransferase and fat mass in a general population of 8-17 years old children. The FLVS II study[J]. Diabetes Metab,2007,33(5):354-359.
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