BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unkno...BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.展开更多
目的 探讨PNPLA3基因多态性与肝癌易感性关系.方法 计算机检索数据库,收集有关PNPLA3基因多态性与肝癌病易感性关系病例对照研究,提取纳人文献的相关数据进行Meta分析,以病例组与对照组PNPLA3各种基因模型的比值比（OR）为效应指标,Egge...目的 探讨PNPLA3基因多态性与肝癌易感性关系.方法 计算机检索数据库,收集有关PNPLA3基因多态性与肝癌病易感性关系病例对照研究,提取纳人文献的相关数据进行Meta分析,以病例组与对照组PNPLA3各种基因模型的比值比（OR）为效应指标,Egger＇s检验和Bgger＇s检验偏倚.结果 共8篇研究符合纳入标准,累计病例数1266例,对照组3529例.Meta分析表明PNPLA3基因多态性与肝癌病易感性有明显关联性.结论 PNPLA3基因多态性与肝癌病易感性明显关联性[GG vs CC：OR=3.05,95％CI：2.42～3.86;CG vs CC：OR =1.30,95％CI：1.13 ～1.50;CG/GG vs CC：OR =1.39,95％CI：1.23～1.57;GG vs CG/CC：OR=2.90,95％CI：2.32～3.63].展开更多
目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照...目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照组,检测各组PNPLA3、Sort1基因多态性。结果 PNPLA3基因rs738409位点检测出CC、CG、GG三种基因型,Sort1基因rs646776位点检测出CC、TC、TT三种基因型;病例组PNPLA3基因GG型和等位基因G的比例分布为23.64%和45.45%,明显高于无肝病嗜酒组和对照组(P<0.05);各组Sort1基因多态性分布差异比较无统计学意义(P>0.05);病例组不同PNPLA3基因型患者甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density liptein cholesterol,HDL-C)和低密度脂蛋白胆固醇(Low Density Lipoprotein Chesterol,LDL-C)比较差异无统计学意义(P>0.05);病例组Sort1基因TT型患者TG为1.61±0.30mmol/L,高于CC+CT型患者,而HDL-C为1.80±0.65mmol/L,低于CC+CT型患者(P<0.05)。结论 PNPLA3基因多态性与酒精性肝病易感性有一定关系,Sort1基因多态性与酒精性肝病易感性无明显关系,但与患者的血脂水平具有一定的相关性。展开更多
AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NA...AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.展开更多
Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variouss...Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variousstudies have established a strong link between the 148 isoleucine to methionine protein variant(I148M) of PNPLA3 and liver diseases,including nonalcoholic fatty liver disease(NAFLD).However,detailed demographic and ethnic characteristics of the I148 M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated.The present review summarizes the current knowledge on the association between the PNPLA3 I148 M variant and NAFLD,and especially its role in the development of nonalcoholic fatty liver fibrosis.First,we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M in the development of nonalcoholic fatty liver fibrosis,and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network.Finally,we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.展开更多
基金Supported by the Faculty of Medicine,Ramathibodi Hospital,Mahidol University。
文摘BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.
文摘目的 探讨PNPLA3基因多态性与肝癌易感性关系.方法 计算机检索数据库,收集有关PNPLA3基因多态性与肝癌病易感性关系病例对照研究,提取纳人文献的相关数据进行Meta分析,以病例组与对照组PNPLA3各种基因模型的比值比（OR）为效应指标,Egger＇s检验和Bgger＇s检验偏倚.结果 共8篇研究符合纳入标准,累计病例数1266例,对照组3529例.Meta分析表明PNPLA3基因多态性与肝癌病易感性有明显关联性.结论 PNPLA3基因多态性与肝癌病易感性明显关联性[GG vs CC：OR=3.05,95％CI：2.42～3.86;CG vs CC：OR =1.30,95％CI：1.13 ～1.50;CG/GG vs CC：OR =1.39,95％CI：1.23～1.57;GG vs CG/CC：OR=2.90,95％CI：2.32～3.63].
文摘目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照组,检测各组PNPLA3、Sort1基因多态性。结果 PNPLA3基因rs738409位点检测出CC、CG、GG三种基因型,Sort1基因rs646776位点检测出CC、TC、TT三种基因型;病例组PNPLA3基因GG型和等位基因G的比例分布为23.64%和45.45%,明显高于无肝病嗜酒组和对照组(P<0.05);各组Sort1基因多态性分布差异比较无统计学意义(P>0.05);病例组不同PNPLA3基因型患者甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density liptein cholesterol,HDL-C)和低密度脂蛋白胆固醇(Low Density Lipoprotein Chesterol,LDL-C)比较差异无统计学意义(P>0.05);病例组Sort1基因TT型患者TG为1.61±0.30mmol/L,高于CC+CT型患者,而HDL-C为1.80±0.65mmol/L,低于CC+CT型患者(P<0.05)。结论 PNPLA3基因多态性与酒精性肝病易感性有一定关系,Sort1基因多态性与酒精性肝病易感性无明显关系,但与患者的血脂水平具有一定的相关性。
基金Supported by State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491 and No.81470840+1 种基金100 Talents Program,No.XBR2011007hProgram of the Shanghai Committee of Science and Technology,No.09140903500 and No.13ZR14267
文摘AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.
基金Supported by National Natural Science Foundation of China No.81170337/H0304
文摘Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variousstudies have established a strong link between the 148 isoleucine to methionine protein variant(I148M) of PNPLA3 and liver diseases,including nonalcoholic fatty liver disease(NAFLD).However,detailed demographic and ethnic characteristics of the I148 M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated.The present review summarizes the current knowledge on the association between the PNPLA3 I148 M variant and NAFLD,and especially its role in the development of nonalcoholic fatty liver fibrosis.First,we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M in the development of nonalcoholic fatty liver fibrosis,and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network.Finally,we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.
