目的探讨葡萄糖激酶调节蛋白（GCKR）基因rs80094多态性与新疆维吾尔族高尿酸血症的关系。方法采用病例,对照研究方法，选择维吾尔族高尿酸血症患者1026例和正常对照1030名。采用Sequenom Mass ARRAY系统对GCKR基因rs780094进行基因分...目的探讨葡萄糖激酶调节蛋白（GCKR）基因rs80094多态性与新疆维吾尔族高尿酸血症的关系。方法采用病例,对照研究方法，选择维吾尔族高尿酸血症患者1026例和正常对照1030名。采用Sequenom Mass ARRAY系统对GCKR基因rs780094进行基因分型，比较高尿酸血症组和正常对照组rs780094基因型与等位基因分布频率差异：比较高尿酸血症组rs780094不同基因型与血压、血脂及血糖的关系；采用logistic回归分析m780094位点与新疆维吾尔族人群高尿酸血症的关系。结果GCKR基因m780094位点G／G、A／G、A／A三种基因型及G、A两种等位基因在高尿酸血症组和对照组分布差异有统计学意义（P〈0．05）。GCKR基因rs780094显性模式（OR=1．295，95％CI 1．078～1．554，P=0．006）及隐性模式（OR=1．284，95％ CI 1．024—1．611，P=0．030）下可见与高尿酸血症的相关趋势。高尿酸血症组GCKR基因rs80094位点GG与AA＋AG基因型比较，收缩压、舒张压及总胆固醇水平较低（P〈0．05）。经调整单因素分析有显著性差异的混杂因素后．多因素条件logistic回归分析提示GCKR基因rs780094A／A及A／G基因型是维吾尔族高尿酸血症患病的危险因素（OR=1．355，95％CI 1．094—1．679，P=0．005）。结论在新疆维吾尔族人群中,GCKR基因rs780094多态性与高尿酸血症相关，A／A及A／G基因型可能是该人群高尿酸血症发生的危险因素。展开更多
Objective To investigate the relationship between glucokinase regulator protein(GCKR)gene polymorphism rs780094 and hyperuricemia in Uygur in Xinjiang.Methods A case-control study including 1 026 patients with hyperur...Objective To investigate the relationship between glucokinase regulator protein(GCKR)gene polymorphism rs780094 and hyperuricemia in Uygur in Xinjiang.Methods A case-control study including 1 026 patients with hyperuricemia and 1 030 normal subjects was conducted.All the subjects were genotyped for GCKR展开更多
Non-alcoholic fatty liver disease(NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis...Non-alcoholic fatty liver disease(NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),fibrosis, cirrhosis, and hepatocellular carcinoma. One of the key challenges in NAFLD is identifying which patients will progress. Epidemiological and genetic studies indicate a strong pattern of heritability that may explain some of the variability in NAFLD phenotype and risk of progression. To date, at least three common genetic variants in the PNPLA3, TM6 SF2, and GCKR genes have been robustly linked to NAFLD in the population. The function of these genes revealed novel pathways implicated in both the development and progression of NAFLD. In addition,candidate genes previously implicated in NAFLD pathogenesis have also been identified as determinants or modulators of NAFLD phenotype including genes involved in hepatocellular lipid handling, insulin resistance,inflammation, and fibrogenesis. This article will review the current understanding of the genetics underpinning the development of hepatic steatosis and the progression of NASH. These newly acquired insights may transform our strategy to risk-stratify patients with NAFLD and to identify new potential therapeutic targets.展开更多
Non-alcoholic fatty liver disease(NAFLD)is estimated to affect 25%of the worldwide population,and is the leading cause of chronic liver disease in developed countries.Genetic research on NAFLD has included heritabilit...Non-alcoholic fatty liver disease(NAFLD)is estimated to affect 25%of the worldwide population,and is the leading cause of chronic liver disease in developed countries.Genetic research on NAFLD has included heritability studies,candidate gene studies,familial aggregation studies,and genome-wide association studies(GWAS).Next-generation sequencing approaches,such as whole-genome sequencing and whole-exon sequencing,are emerging as the post-GWAS era of genetic research.However,GWAS remains more practical for elucidating the genetic factors related to NAFLD,which is affected by thousands of common genetic variants and does not follow Mendelian inheritance.In the present review,we summarize the current knowledge regarding five GWAS-identified genetic loci that are associated with NAFLD.We also discuss the relationships between NAFLD-predisposing polymorphisms and cardiovascular disease,and potential applications for these identified genetic loci.展开更多
文摘目的探讨葡萄糖激酶调节蛋白（GCKR）基因rs80094多态性与新疆维吾尔族高尿酸血症的关系。方法采用病例,对照研究方法，选择维吾尔族高尿酸血症患者1026例和正常对照1030名。采用Sequenom Mass ARRAY系统对GCKR基因rs780094进行基因分型，比较高尿酸血症组和正常对照组rs780094基因型与等位基因分布频率差异：比较高尿酸血症组rs780094不同基因型与血压、血脂及血糖的关系；采用logistic回归分析m780094位点与新疆维吾尔族人群高尿酸血症的关系。结果GCKR基因m780094位点G／G、A／G、A／A三种基因型及G、A两种等位基因在高尿酸血症组和对照组分布差异有统计学意义（P〈0．05）。GCKR基因rs780094显性模式（OR=1．295，95％CI 1．078～1．554，P=0．006）及隐性模式（OR=1．284，95％ CI 1．024—1．611，P=0．030）下可见与高尿酸血症的相关趋势。高尿酸血症组GCKR基因rs80094位点GG与AA＋AG基因型比较，收缩压、舒张压及总胆固醇水平较低（P〈0．05）。经调整单因素分析有显著性差异的混杂因素后．多因素条件logistic回归分析提示GCKR基因rs780094A／A及A／G基因型是维吾尔族高尿酸血症患病的危险因素（OR=1．355，95％CI 1．094—1．679，P=0．005）。结论在新疆维吾尔族人群中,GCKR基因rs780094多态性与高尿酸血症相关，A／A及A／G基因型可能是该人群高尿酸血症发生的危险因素。
文摘Objective To investigate the relationship between glucokinase regulator protein(GCKR)gene polymorphism rs780094 and hyperuricemia in Uygur in Xinjiang.Methods A case-control study including 1 026 patients with hyperuricemia and 1 030 normal subjects was conducted.All the subjects were genotyped for GCKR
基金supported by an Alan Hofmann Clinical and Translational Research Award from AASLD
文摘Non-alcoholic fatty liver disease(NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),fibrosis, cirrhosis, and hepatocellular carcinoma. One of the key challenges in NAFLD is identifying which patients will progress. Epidemiological and genetic studies indicate a strong pattern of heritability that may explain some of the variability in NAFLD phenotype and risk of progression. To date, at least three common genetic variants in the PNPLA3, TM6 SF2, and GCKR genes have been robustly linked to NAFLD in the population. The function of these genes revealed novel pathways implicated in both the development and progression of NAFLD. In addition,candidate genes previously implicated in NAFLD pathogenesis have also been identified as determinants or modulators of NAFLD phenotype including genes involved in hepatocellular lipid handling, insulin resistance,inflammation, and fibrogenesis. This article will review the current understanding of the genetics underpinning the development of hepatic steatosis and the progression of NASH. These newly acquired insights may transform our strategy to risk-stratify patients with NAFLD and to identify new potential therapeutic targets.
基金This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Ministry of Science&ICT(NRF-2020M3A9E4038694).
文摘Non-alcoholic fatty liver disease(NAFLD)is estimated to affect 25%of the worldwide population,and is the leading cause of chronic liver disease in developed countries.Genetic research on NAFLD has included heritability studies,candidate gene studies,familial aggregation studies,and genome-wide association studies(GWAS).Next-generation sequencing approaches,such as whole-genome sequencing and whole-exon sequencing,are emerging as the post-GWAS era of genetic research.However,GWAS remains more practical for elucidating the genetic factors related to NAFLD,which is affected by thousands of common genetic variants and does not follow Mendelian inheritance.In the present review,we summarize the current knowledge regarding five GWAS-identified genetic loci that are associated with NAFLD.We also discuss the relationships between NAFLD-predisposing polymorphisms and cardiovascular disease,and potential applications for these identified genetic loci.
