痛风是由高尿酸血症引发的一种常见炎性关节炎,受遗传因素和环境因素共同作用。早期研究表明,PRPS1和HPRT1等单基因稀有突变会引起嘌呤合成代谢紊乱,从而引发高尿酸血症和痛风。近年来,全基因组关联分析(Genome-wide association studie...痛风是由高尿酸血症引发的一种常见炎性关节炎,受遗传因素和环境因素共同作用。早期研究表明,PRPS1和HPRT1等单基因稀有突变会引起嘌呤合成代谢紊乱,从而引发高尿酸血症和痛风。近年来,全基因组关联分析(Genome-wide association studies,GWAS)已检出多个导致高尿酸血症和痛风的易感位点及相关候选基因。其中SLC2A9、SLC22A11和SLC22A12基因功能缺失性突变可引起遗传性低尿酸血症,而过表达则会加强尿酸的重吸收。ABCG2、SLC17A1和SLC17A3基因功能缺陷型变异会降低肾脏和肠道对尿酸的排泄量。因此,诱发尿酸排泄障碍(高重吸收和低排泄)的基因变异是影响高尿酸血症和痛风的主要遗传因素。另外,抑制-激活生长因子系统、转录因子、细胞骨架以及基因和环境的互作等因素也一定程度影响血液尿酸水平。在中国汉族人群中,两个新发现的易感基因RFX3和KCNQ1可能造成免疫应答受损和胰岛B细胞功能缺陷,从而直接或间接引起高尿酸酸血症和痛风。本文系统综述了高尿酸血症和痛风的遗传学研究,以促进人们对高尿酸血症和痛风发病机理的理解。展开更多
Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger...Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger PBC exists,the etiologies for PSC and AIH remain unknown.Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases,their associations with environmental triggers and the subsequent implications have been difficult to elucidate.While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4(CTLA-4) have been suggested as genetic susceptibility factors for all three disorders,we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC,where Novosphingobium aromaticivorans,an ubiquitous alphaproteobacterium,has recently been specifically associated with the pathogenesis of this devastating liver disease.Ultimately,the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers,establish infection and damage respective target organs.展开更多
There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a...There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.展开更多
目的:对关节病型银屑病与强直性脊柱炎的易感基因进行关联分析,以期发现共同的易感基因。方法:以379例关节病型银屑病(PsA)、595例寻常型银屑病(PsV)及806例健康对照为样本,以Sequenom MassA RRAY系统为平台,对全基因组关联研究发现的...目的:对关节病型银屑病与强直性脊柱炎的易感基因进行关联分析,以期发现共同的易感基因。方法:以379例关节病型银屑病(PsA)、595例寻常型银屑病(PsV)及806例健康对照为样本,以Sequenom MassA RRAY系统为平台,对全基因组关联研究发现的强直性脊柱炎的9个易感基因SNP位点进行基因分型和数据分析。结果:ERAP1基因(rs27037,P=6.66×10-5,OR:1.43)、21q22.2(rs2242944,P=1.07×10-3,OR:0.73)及IL23R基因(rs1004819,P=4.58×10-3,OR:1.28)与PsA相关。ERAP1(rs27037,P=1.56×10-4,OR:1.35)与PsV相关。ERAP1基因对于PsA和PsV的患病风险无差异。IL23R基因(rs1004819)及21q22.2(rs2242944)在PsA和PsV患病风险上存在中等程度的异质性(I2值分别为57.41和71.20),但P值无明显差异(>0.05)。IL23R基因(rs11209032,P=1.57×10-3,OR:1.52)与PsA脊柱炎相关。结论:ERAP1基因、21q22.2区域及IL23R基因是PsA与强直性脊柱炎共有的易感基因。展开更多
文摘痛风是由高尿酸血症引发的一种常见炎性关节炎,受遗传因素和环境因素共同作用。早期研究表明,PRPS1和HPRT1等单基因稀有突变会引起嘌呤合成代谢紊乱,从而引发高尿酸血症和痛风。近年来,全基因组关联分析(Genome-wide association studies,GWAS)已检出多个导致高尿酸血症和痛风的易感位点及相关候选基因。其中SLC2A9、SLC22A11和SLC22A12基因功能缺失性突变可引起遗传性低尿酸血症,而过表达则会加强尿酸的重吸收。ABCG2、SLC17A1和SLC17A3基因功能缺陷型变异会降低肾脏和肠道对尿酸的排泄量。因此,诱发尿酸排泄障碍(高重吸收和低排泄)的基因变异是影响高尿酸血症和痛风的主要遗传因素。另外,抑制-激活生长因子系统、转录因子、细胞骨架以及基因和环境的互作等因素也一定程度影响血液尿酸水平。在中国汉族人群中,两个新发现的易感基因RFX3和KCNQ1可能造成免疫应答受损和胰岛B细胞功能缺陷,从而直接或间接引起高尿酸酸血症和痛风。本文系统综述了高尿酸血症和痛风的遗传学研究,以促进人们对高尿酸血症和痛风发病机理的理解。
基金Supported by a Grant from the Deutsche Forschungsgemein-schaft(MA 2621/2-1)the Lupus Research Institute and by Award Number R01DK084054 from the National Institute of Diabetes and Digestive and Kidney Diseases
文摘Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger PBC exists,the etiologies for PSC and AIH remain unknown.Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases,their associations with environmental triggers and the subsequent implications have been difficult to elucidate.While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4(CTLA-4) have been suggested as genetic susceptibility factors for all three disorders,we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC,where Novosphingobium aromaticivorans,an ubiquitous alphaproteobacterium,has recently been specifically associated with the pathogenesis of this devastating liver disease.Ultimately,the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers,establish infection and damage respective target organs.
文摘There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
文摘目的:对关节病型银屑病与强直性脊柱炎的易感基因进行关联分析,以期发现共同的易感基因。方法:以379例关节病型银屑病(PsA)、595例寻常型银屑病(PsV)及806例健康对照为样本,以Sequenom MassA RRAY系统为平台,对全基因组关联研究发现的强直性脊柱炎的9个易感基因SNP位点进行基因分型和数据分析。结果:ERAP1基因(rs27037,P=6.66×10-5,OR:1.43)、21q22.2(rs2242944,P=1.07×10-3,OR:0.73)及IL23R基因(rs1004819,P=4.58×10-3,OR:1.28)与PsA相关。ERAP1(rs27037,P=1.56×10-4,OR:1.35)与PsV相关。ERAP1基因对于PsA和PsV的患病风险无差异。IL23R基因(rs1004819)及21q22.2(rs2242944)在PsA和PsV患病风险上存在中等程度的异质性(I2值分别为57.41和71.20),但P值无明显差异(>0.05)。IL23R基因(rs11209032,P=1.57×10-3,OR:1.52)与PsA脊柱炎相关。结论:ERAP1基因、21q22.2区域及IL23R基因是PsA与强直性脊柱炎共有的易感基因。
