中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

非酒精性脂肪性肝病相关易感基因及其在发病机制中的作用

宣世英 袁晨 芦琳琳 辛永宁

引用本文:
Citation:

非酒精性脂肪性肝病相关易感基因及其在发病机制中的作用

DOI: 10.3969/j.issn.1001-5256.2016.03.009
详细信息
  • 中图分类号: R575.5

Research advances in susceptibility genes and their role in the pathogenesis of nonalcoholic fatty liver disease

  • 摘要: 非酒精性脂肪性肝病(NAFLD)发病率逐年增高并呈低龄化趋势,严重增加个人及社会经济负担。作为一种遗传-代谢-环境相关疾病,遗传因素在NAFLD发生发展中起着尤为重要的作用。随着全基因组关联研究技术的广泛应用,对NAFLD遗传易感基因的研究不断取得新的进展。总结国内外现有研究成果,以其遗传易感基因多态性为切入点,探讨影响NAFLD的发病因素及内在机制。

     

  • [1]GRANDONE A,MARZUILLO P,PERRONE L,et al.Iron metabolism dysregulation and cognitive dysfunction in pediatric obesity:is there a connection?[J].Nutrients,2015,7(11):9163-9170.
    [2]DAY CP.NASH-related liver failure:one hit too many?[J].Am J Gastroenterol,2002,97(8):1872-1874.
    [3]TILG H,MOSCHEN AR.Evolution of inflammation in nonalcoholic fatty liver disease:the multiple parallel hits hypothesis[J].Hepatology,2010,52(5):1836-1846.
    [4]ZHANG CX,GUO LK,GUO XF.Interaction of polymorphisms of Leptin receptor gene Gln223Arg,Mn SOD9Ala/Val genes and smoking in nonalcoholic fatty liver disease[J].J Hygiene Res,2014,43(5):724-731.(in Chinese)张超贤,郭李柯,郭晓凤.瘦素受体基因Gln223Arg、锰超氧化物歧化酶9Ala/Val基因多态性与吸烟的交互作用和非酒精性脂肪性肝病关系[J].卫生研究,2014,43(5):724-731.
    [5]SWELLAM M,HAMDY N.Association of nonalcoholic fatty liver disease with a single nucleotide polymorphism on the gene encoding leptin receptor[J].IUBMB Life,2012,64(2):180-186.
    [6]LU H,SUN J,SUN L,et al.Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China[J].J Gastroenterol Hepatol,2009,24(2):228-232.
    [7]ZAIN SM,MOHAMED R,MAHADEVA S,et al.A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease[J].Hum Genet,2012,131(7):1145-1152.
    [8]LI YL,YANG M,MENG XD,et al.The relationship of leptin and adiponectin with insulin resistance in nonalcoholic fatty liver disease[J].Chin J Hepatol,2010,18(6):459-462.(in Chinese)李异玲,杨淼,孟晓丹,等.非酒精性脂肪性肝病患者血清瘦素和脂联素与胰岛素抵抗的关系[J].中华肝脏病杂志,2010,18(6):459-462.
    [9]GUPTA AC,MISRA R,SAKHUJA P,et al.Association of adiponectin gene functional polymorphisms(-11377C/G and+45T/G)with nonalcoholic fatty liver disease[J].Gene,2012,496(1):63-67.
    [10]MENTA A,MEYRE D,LANKTREE MB,et al.Causal relationship between adiponectin and metabolic traits:a Mendelian randomization study in a multiethnic population[J].PLo S One,2013,8(6):e66808.
    [11]HASHEMI M,HANAFI BOJD H,ESKANDARI NASAB E,et al.Association of adiponectin rs1501299 and rs266729 gene polymorphisms with nonalcoholic fatty liver disease[J].Hepat Mon,2013,13(5):e9527.
    [12]GU YJ,WANG Q.Relationship of adiponectin receptor gene polymorphisms with nonalcoholic fatty liver disease[J].Chin J Dig,2011,31(5):343-344.(in Chinese)古艳芳,王琦.脂联素受体基因多态性与非酒精性脂肪性肝病的关系[J].中华消化杂志,2011,31(5):343-344.
    [13]HUANG Q,YANG TL,TANG BS,et al.Two novel functional single nucleotide polymorphisms of ADRB3 are associated with type 2diabetes in the Chinese population[J].J Clin Endocrinol Metab,2013,98(7):e1272-e1277.
    [14]ZHANG CX,GUO LK,GUO XF.Correlation of cigarette smoking and the polymorphisms ofβ3-adrenergic receptor gene Trp64Arg,MnSOD9Ala/Val genes with nonalcoholic fatty liver disease[J].J Xi'an Jiaotong Univ:Med Sci,2015,36(1):106-121.(in Chinese)张超贤,郭李柯,郭晓凤.吸烟和β3-肾上腺素能受体基因Trp64Arg、锰超氧化物歧化酶9Ala/Val基因多态性与非酒精性脂肪性肝病的相关性[J].西安交通大学学报:医学版,2015,36(1):106-121.
    [15]PETERSEN KF,DUFOUR S,HARIRI A,et al.Apolipoprotein C3gene variants in nonalcoholic fatty liver disease[J].N Engl J Med,2010,362(12):1082-1089.
    [16]NIU TH,JIANG M,LIU HG,et al.Association between APOC3 promoter region polymorphisms and non-alcoholic fatty liver disease[J].Chin J Hepatol,2014,22(5):374-379.(in Chinese)牛同红,姜曼,刘昊刚,等.载脂蛋白C3启动子区基因多态性与非酒精性脂肪性肝病的相关性[J].中华肝脏病杂志,2014,22(5):374-379.
    [17]POLLEX RL,BAN MR,YOUNG TK,et al.Association between the-455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample[J].BMC Med Genet,2007,8:80.
    [18]VALENTI L,NOBILI V,AL-SERRIl A,et al.The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3I148M genotype in patients with nonalcoholic fatty liver[J].J Hepatol,2011,55(6):1409-1414.
    [19]NIU TH,JIANG M,XIN YN,et al.Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population[J].World J Gastroenterol,2014,20(13):3655-3662.
    [20]VERRIJKEN A,BECKERS S,FRANCQUE S,et al.A gene variant of PNPLA3,but not of APOC3,is associated with histological parameters of NAFLD in an obese population[J].Obesity(Silver Spring),2013,21(10):2138-2145.
    [21]HYYSALO J,STOJKOVIC I,KOTRONEN A,et al.Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease[J].J Gastroenterol Hepatol,2012,27(5):951-956.
    [22]SENTINELLI F,ROMEO S,MAGLIO C,et al.Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis,lipid profile and insulin resistance in obese Southern Europeans[J].Lipids Health Dis,2011,10:93.
    [23] ZHANG H,CHEN L,XIN Y,et al.Apolipoprotein c3 gene polymorphisms are not a risk factor for developing non-alcoholic Fatty liver disease:a meta-analysis[J].Hepat Mon,2014,14(10):e23100.
    [24]PUPPALA J,BHRUGUMALLA S,KUMAR A,et al.Apolipoprotein C3 gene polymorphisms in Southern Indian patients with nonalcoholic fatty liver disease[J].Indian J Gastroenterol,2014,33(6):524-529.
    [25]JIANG X,BAI XY,WU HJ.Role of peroxisome proliferator-activated receptors in the pathogenesis of nonalcoholic fatty liver disease[J].Progr physiolog Sci,2015,46(3):220-226.(in Chinese)姜潇,白晓彦,伍会健.PPARs在非酒精性脂肪性肝病发病机制中的作用[J].生理科学进展,2015,46(3):220-226.
    [26]CHEN S,LI Y,LI S,et al.A Val227Ala substitution in the peroxisome proliferator activated receptor alpha(PPAR alpha)gene associated with non-alcoholic fatty liver disease and decreased waist circumference and waist-to-hip ratio[J].J Gastroenterol Hepatol,2008,23(9):1415-1418.
    [27]DONGIOVANNI P,RAMETTA R,FRACANZANI AL,et al.Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease:a case control study[J].BMC Gastroenterol,2010,10:102.
    [28]ROMEO S,KOZLITINA J,XING C,et al.Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease[J].Nat Genet,2008,40(12):1461-1465.
    [29] ZHANG DD,JIANG M,YIN YN,et al.Construction of lentivirus vectors containing PNPLA3 gene and overexpression of PNPLA3 in Huh-7 cells[J].Chin J Hepatol,2013,21(3):236-238.(in Chinese)张丁丁,姜曼,辛永宁,等.PNPLA3 rs738409基因多态性与非酒精性脂肪性肝病遗传易感性的关系[J].中华肝脏病杂志,2013,21(3):236-238.
    [30]XU J,XIN YN,LYU WH,et al.Polymorphism rs738409 in PNPLA3 is associated with inherited susceptibility to non-alcoholic fatty liver disease[J].Chin J Hepatol,2013,21(8):619-623.徐静,辛永宁,吕维红,等.PNPLA3 rs738409基因多态性与非酒精性脂肪性肝病遗传易感性的关系[J].中华肝脏病杂志,2013,21(8):619-623.
    [31]MARZUILLO P,GRANDONE A,PERRONE L,et al.Weight loss allows the dissection of the interaction between abdominal fat and PNPLA3(adiponutrin)in the liver damage of obese children[J].J Hepatol,2013,59(5):1143-1144.
    [32]MAHDESSIAN H,TAXIARCHIS A,POPOV S,et al.TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content[J].Proc Natl Acad Sci U S A,2014,111(24):8913-8918.
    [33]KOZLITINA J,SMAGRIS E,STENDER S,et al.Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease[J].Nat Genet,2014,46(4):352-356.
    [34]PIROLA CJ,SOOKOIAN S.The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver:a Meta-analysis[J].Hepatology,2015,62(6):1742-1756.
    [35]LI L,WANG SJ,SHI K,et al.Correlation between MTP-493G>T polymorphism and non-alcoholic fatty liver disease risk:a Meta-analysis[J].Genet Mol Res,2014,13(4):10150-10161.
    [36]PENG XE,WU YL,LU QQ,et al.MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population[J].Liver Int,2014,34(1):118-128.
    [37]MEHTA R,BIRERDINC A,YOUNOSSI ZM.Host genetic variants in obesity-related nonalcoholic fatty liver disease[J].Clin Liver Dis,2014,18(1):249-267.
    [38]OTT C,ROSS K,STRAUB S,et al.Sam50 functions in mitochondrial intermembrane space bridging and biogenesis of respiratory complexes[J].Mol Cell Biol,2012,32(6):1173-1188.
    [39]OTT C,DORSCH E,FRAUNHOLZ M,et al.Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits[J].PLo S One,2015,10(3):e0120213.
    [40]KITAMOTO T,KITAMOTO A,YONEDA M,et al.Genome-wide scan revealed that polymorphisms in the PNPLA3,SAMM50,and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan[J].Hum Genet,2013,132(7):783-792.
    [41]BEER NL,TRIBBLE ND,MCCULLOCH LJ,et al.The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver[J].Hum Mol Genet,2009,18(21):4081-4088.
    [42]SPELIOTES EK,YERGES-ARMSTRONG LM,WU J,et al.Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits[J].PLo S Genet,2011,7(3):e1001324.
    [43]BAI LM,MA YZ,WANG QL.Research advances in the roles of TNF-αand leptin in the development and progression of nonalcoholic fatty liver disease[J].Inner Mongolia J Tradit Chin Med,2012,44(9):1086-1089.(in Chinese)白莲梅,马玉珍,王清莲.TNF-α瘦素与非酒精性脂肪性肝病发生发展相关性的研究进展[J].内蒙古医学杂志,2012,44(9):1086-1089.
    [44]NADERI M,YAGHOOTKAR H,TARA F,et al.Tumor necrosis factor-alpha polymorphism at position-238 in preeclampsia[J].Iran Red Crescent Med J,2014,16(1):e11195.
    [45]LIN X,ZHANG Z,CHEN JM,et al.Role of APN and TNF-alpha in type 2 diabetes mellitus complicated by nonalcoholic fatty liver disease[J].Genet Mol Res,2015,14(2):2940-2946.
    [46]PURNOMO HD,MUNDHOFIR FE,KASNO,et al.Combination of aspartate aminotranferase and tumor necrosis factor-alpha as non invasive diagnostic tools for non alcoholic steatohepatitis(NASH)[J].Acta Med Indones,2015,47(1):16-23.
    [47]WANG JK,FENG ZW,LI YC,et al.Association of tumor necrosis factor-alpha gene promoter polymorphism at sites-308 and-238with non-alcoholic fatty liver disease:a meta-analysis[J].J Gastroenterol Hepatol,2012,27(4):670-676.
    [48]CHU H,YANG J,MI S,et al.Tumor necrosis factor-alpha G-308 A polymorphism and risk of coronary heart disease and myocardial infarction:a case-control study and Meta-analysis[J].J Cardiovasc Dis Res,2012,3(2):84-90.
    [49]TOKUSHIGE K,TAKAHURA M,TSUCHIYA-MATSUSHITA N,et al.Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis[J].J Hepatol,2007,46(6):1104-1110.
    [50]VALENTI L,FRACANZANI AL,DONGIOVANNI P,et al.Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease[J].Gastroenterology,2002,122(2):274-280.
    [51]CHENG Y,AN B,JIANG M,et al.Association of tumor necrosis factor-alpha polymorphisms and risk of coronary artery disease in patients with non-alcoholic fatty liver disease[J].Hepat Mon,2015,15(3):e26818.
    [52]MAHMOUD AA,BAKIR AS,SHABANA SS.Serum TGF-beta,Serum MMP-1,and HOMA-IR as non-invasive predictors of fibrosis in Egyptian patients with NAFLD[J].Saudi J Gastroenterol,2012,18(5):327-333.
    [53]ZAIN SM,MOHANED Z,MAHADEVA S,et al.Susceptibility and gene interaction study of the angiotensin II type 1 receptor(AGTR1)gene polymorphisms with non-alcoholic fatty liver disease in a multi-ethnic population[J].PLo S One,2013,8(3):e58538.
    [54]SAZCI A,ERGUL E,AYGUN C,et al.Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis(NASH)[J].Cell Biochem Funct,2008,26(3):291-296.
    [55]WILLEBRORDS J,PEREIRA IV,MAES M,et al.Strategies,models and biomarkers in experimental non-alcoholic fatty liver disease research[J].Prog Lipid Res,2015,59:106-125.
    [56]NUSSBAUM JM,LIU LJ,HASAN SA,et al.Homeostatic generation of reactive oxygen species protects the zebrafish liver from steatosis[J].Hepatology,2013,58(4):1326-1338.
    [57]HSU CC,PAI WY,LAI CY,et al.Genetic characterization and in vivo image analysis of novel zebrafish Danio rerio pigment mutants[J].J Fish Biol,2013,82(5):1671-1683.
    [58]HER GM,PAI WY,LAI CY,et al.Ubiquitous transcription factor YY1 promotes zebrafish liver steatosis and lipotoxicity by inhibiting CHOP-10 expression[J].Biochim Biophys Acta,2013,1831(6):1037-1051.
    [59]THAKUR PC,STUCKENHOLZ C,RIVERA MR,et al.Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish[J].Hepatology,2011,54(2):452-462.
    [60]SHARMA M,MITNALA S,VISHNUBHOTLA RK,et al.The riddle of nonalcoholic fatty liver disease:progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis[J].J Clin Exp Hepatol,2015,5(2):147-158.
    [61]WAN X,XU C,YU C.Role of the NLRP3 inflammasome in the progression of nonalcoholic fatty liver disease to nonalcoholic steatohepatitis[J].Can J Gastroenterol Hepatol,2015.[Epub ahead of print]
  • 加载中
计量
  • 文章访问数:  2162
  • HTML全文浏览量:  42
  • PDF下载量:  1042
  • 被引次数: 0
出版历程
  • 收稿日期:  2015-11-17
  • 出版日期:  2016-03-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回