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New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes
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نویسنده
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sandholm n. ,salem r.m. ,mcknight a.j. ,brennan e.p. ,forsblom c. ,isakova t. ,mckay g.j. ,williams w.w. ,sadlier d.m. ,mäkinen v.-p. ,swan e.j. ,palmer c. ,boright a.p. ,ahlqvist e. ,deshmukh h.a. ,keller b.j. ,huang h. ,ahola a.j. ,fagerholm e. ,gordin d. ,harjutsalo v. ,he b. ,heikkilä o. ,hietala k. ,kytö j. ,lahermo p. ,lehto m. ,lithovius r. ,österholm a.-m. ,parkkonen m. ,pitkäniemi j. ,rosengård-bärlund m. ,saraheimo m. ,sarti c. ,söderlund j. ,soro-paavonen a. ,syreeni a. ,thorn l.m. ,tikkanen h. ,tolonen n. ,tryggvason k. ,tuomilehto j. ,wadén j. ,gill g.v. ,prior s. ,guiducci c. ,mirel d.b. ,taylor a. ,hosseini s.m. ,parving h.-h. ,rossing p. ,tarnow l. ,ladenvall c. ,alhenc-gelas f. ,lefebvre p. ,rigalleau v. ,roussel r. ,tregouet d.-a. ,maestroni a. ,maestroni s. ,falhammar h. ,gu t. ,möllsten a. ,cimponeriu d. ,ioana m. ,mota m. ,mota e. ,serafinceanu c. ,stavarachi m. ,hanson r.l. ,nelson r.g. ,kretzler m. ,colhoun h.m. ,panduru n.m. ,gu h.f. ,brismar k. ,zerbini g. ,hadjadj s. ,marre m. ,groop l. ,lajer m. ,bull s.b. ,waggott d. ,paterson a.d. ,savage d.a. ,bain s.c. ,martin f. ,hirschhorn j.n. ,godson c. ,florez j.c. ,groop p.-h. ,maxwell a.p. ,böger c.a.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 9
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چکیده
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Diabetic kidney disease,or diabetic nephropathy (dn),is a major complication of diabetes and the leading cause of end-stage renal disease (esrd) that requires dialysis treatment or kidney transplantation. in addition to the decrease in the quality of life,dn accounts for a large proportion of the excess mortality associated with type 1 diabetes (t1d). whereas the degree of glycemia plays a pivotal role in dn,a subset of individuals with poorly controlled t1d do not develop dn. furthermore,strong familial aggregation supports genetic susceptibility to dn. however,the genes and the molecular mechanisms behind the disease remain poorly understood,and current therapeutic strategies rarely result in reversal of dn. in the genetics of nephropathy: an international effort (genie) consortium,we have undertaken a meta-analysis of genome-wide association studies (gwas) of t1d dn comprising ~2.4 million single nucleotide polymorphisms (snps) imputed in 6,691 individuals. after additional genotyping of 41 top ranked snps representing 24 independent signals in 5,873 individuals,combined meta-analysis revealed association of two snps with esrd: rs7583877 in the aff3 gene (p = 1.2×10-8) and an intergenic snp on chromosome 15q26 between the genes rgma and mctp2,rs12437854 (p = 2.0×10-9). functional data suggest that aff3 influences renal tubule fibrosis via the transforming growth factor-beta (tgf-β1) pathway. the strongest association with dn as a primary phenotype was seen for an intronic snp in the erbb4 gene (rs7588550,p = 2.1×10-7),a gene with type 2 diabetes dn differential expression and in the same intron as a variant with cis-eqtl expression of erbb4. all these detected associations represent new signals in the pathogenesis of dn. © 2012 sandholm et al.
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آدرس
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folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki,finland,department of biomedical engineering and computational science,aalto university,espoo, Finland, program in medical and population genetics,broad institute,cambridge,ma,united states,endocrine research unit,department of endocrinology,children's hospital,boston,ma,united states,department of medicine,harvard medical school,boston,ma, United States, nephrology research,centre for public health,queen's university of belfast,belfast, United Kingdom, diabetes research centre,conway institute,school of medicine and medical sciences,university college dublin,dublin,ireland,mater misericordiae hospital,dublin, Ireland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, division of nephrology and hypertension,university of miami,miami,fl, United States, nephrology research,centre for public health,queen's university of belfast,belfast, United Kingdom, department of medicine,harvard medical school,boston,ma,united states,center for human genetic research,massachusetts general hospital,boston,ma, United States, diabetes research centre,conway institute,school of medicine and medical sciences,university college dublin,dublin,ireland,mater misericordiae hospital,dublin, Ireland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki,finland,institute of clinical medicine,department of internal medicine,biocenter oulu and clinical research center,university of oulu,oulu, Finland, nephrology research,centre for public health,queen's university of belfast,belfast, United Kingdom, program in medical and population genetics,broad institute,cambridge,ma,united states,endocrine research unit,department of endocrinology,children's hospital,boston,ma, United States, department of medicine,university of toronto,toronto, Canada, department of clinical sciences,diabetes,and endocrinology,skåne university hospital,lund university,malmö, Sweden, wellcome trust centre for molecular medicine,university of dundee,dundee, United Kingdom, computer science,eastern michigan university,ypsilanti,mi, United States, division of nephrology,internal medicine,university of michigan,ann arbor,mi, United States, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki,finland,diabetes prevention unit,national institute for health and welfare,helsinki, Finland, division of matrix biology,department of medical biochemistry and biophysics,karolinska institutet,stockholm, Sweden, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,department of ophthalmology,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,department of ophthalmology,helsinki university central hospital,helsinki, Finland, institute for molecular medicine finland,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, division of matrix biology,department of medical biochemistry and biophysics,karolinska institutet,stockholm, Sweden, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, hjelt institute,department of public health,university of helsinki,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, hjelt institute,department of public health,university of helsinki,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, unit for sports and exercise medicine,institute of clinical medicine,university of helsinki, Finland, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, division of matrix biology,department of medical biochemistry and biophysics,karolinska institutet,stockholm, Sweden, diabetes prevention unit,national institute for health and welfare,helsinki,finland,south ostrobothnia central hospital,seinäjoki,finland,red recava grupo rd06/0014/0015,hospital universitario la paz,madrid,spain,centre for vascular prevention,danube-university krems,krems, Austria, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki, Finland, diabetes endocrine unit,clinical sciences centre,aintree university hospital,university of liverpool,liverpool, United Kingdom, institute of life sciences,swansea university,swansea, United Kingdom, program in medical and population genetics,broad institute,cambridge,ma, United States, program in medical and population genetics,broad institute,cambridge,ma, United States, program in medical and population genetics,broad institute,cambridge,ma,united states,center for human genetic research,massachusetts general hospital,boston,ma, United States, institute of medical science,university of toronto,toronto,canada,program in genetics and genome biology,hospital for sick children,toronto, Canada, department of medical endocrinology,university hospital of copenhagen,copenhagen,denmark,faculty of health sciences,university of aarhus,aarhus, Denmark, faculty of health sciences,university of aarhus,aarhus,denmark,steno diabetes center,gentofte, Denmark, faculty of health sciences,university of aarhus,aarhus,denmark,steno diabetes center,gentofte, Denmark, department of clinical sciences,diabetes,and endocrinology,skåne university hospital,lund university,malmö, Sweden, inserm u872,paris-descartes university,pierre and marie curie university,paris, France, chu sart tilman,liège, Belgium, chu bordeaux,bordeaux, France, ap-hp,hôpital bichat,diabetology endocrinology nutrition,paris,france,université paris diderot,sorbonne paris cité,umr 738,paris,france,inserm,umr872,equipe 2,centre de recherche des cordeliers,paris, France, inserm umr-s 937,ican institute for cardiometabolism and nutrition,pierre and marie curie university,paris, France, complications of diabetes unit,division of metabolic and cardiovascular sciences,san raffaele scientific institute,milano, Italy, complications of diabetes unit,division of metabolic and cardiovascular sciences,san raffaele scientific institute,milano, Italy, department of molecular medicine and surgery,karolinska institutet,stockholm,sweden,department of endocrinology,metabolism,and diabetes,karolinska university hospital,stockholm, Sweden, department of molecular medicine and surgery,karolinska institutet,stockholm, Sweden, department of clinical sciences,paediatrics,umeå university,umeå, Sweden, genetics department,bucharest university,bucharest, Romania, university of medicine and pharmacy of craiova,craiova, Romania, university of medicine and pharmacy of craiova,craiova, Romania, university of medicine and pharmacy of craiova,craiova, Romania, carol davila university of medicine and pharmacy,bucharest, Romania, genetics department,bucharest university,bucharest, Romania, diabetes epidemiology and clinical research section,niddk,phoenix,az, United States, diabetes epidemiology and clinical research section,niddk,phoenix,az, United States, internal medicine,center for computational medicine and bioinformatics,university of michigan,ann arbor,mi, United States, wellcome trust centre for molecular medicine,university of dundee,dundee, United Kingdom, carol davila university of medicine and pharmacy,bucharest, Romania, department of molecular medicine and surgery,karolinska institutet,stockholm, Sweden, department of molecular medicine and surgery,karolinska institutet,stockholm,sweden,department of endocrinology,metabolism,and diabetes,karolinska university hospital,stockholm, Sweden, complications of diabetes unit,division of metabolic and cardiovascular sciences,san raffaele scientific institute,milano, Italy, chu poitiers-endocrinology,university of poitiers,poitiers,france,inserm cic0802,chu poitiers,poitiers, France, ap-hp,hôpital bichat,diabetology endocrinology nutrition,paris,france,université paris diderot,sorbonne paris cité,umr 738,paris,france,inserm,u695 (genetic determinants of type 2 diabetes and its vascular complications),paris, France, department of clinical sciences,diabetes,and endocrinology,skåne university hospital,lund university,malmö, Sweden, steno diabetes center,gentofte, Denmark, prosserman centre for health research,samuel lunenfeld research institute,toronto,canada,division of biostatistics,dalla lana school of public health,university of toronto,toronto, Canada, prosserman centre for health research,samuel lunenfeld research institute,toronto, Canada, program in genetics and genome biology,hospital for sick children,toronto,canada,division of biostatistics,dalla lana school of public health,university of toronto,toronto, Canada, nephrology research,centre for public health,queen's university of belfast,belfast, United Kingdom, institute of life sciences,swansea university,swansea, United Kingdom, diabetes research centre,conway institute,school of medicine and medical sciences,university college dublin,dublin,ireland,mater misericordiae hospital,dublin, Ireland, program in medical and population genetics,broad institute,cambridge,ma,united states,endocrine research unit,department of endocrinology,children's hospital,boston,ma,united states,department of medicine,harvard medical school,boston,ma, United States, diabetes research centre,conway institute,school of medicine and medical sciences,university college dublin,dublin,ireland,mater misericordiae hospital,dublin, Ireland, program in medical and population genetics,broad institute,cambridge,ma,united states,department of medicine,harvard medical school,boston,ma,united states,center for human genetic research,massachusetts general hospital,boston,ma, United States, folkhälsan institute of genetics,folkhälsan research center,biomedicum helsinki,helsinki,finland,division of nephrology,department of medicine,helsinki university central hospital,helsinki,finland,baker idi heart and diabetes institute,melbourne, Australia, nephrology research,centre for public health,queen's university of belfast,belfast,united kingdom,regional nephrology unit,belfast city hospital,belfast, United Kingdom, university hospital regensburg, Germany
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Authors
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