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A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes
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نویسنده
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maeda s. ,kobayashi m.-a. ,araki s.-i. ,babazono t. ,freedman b.i. ,bostrom m.a. ,cooke j.n. ,toyoda m. ,umezono t. ,tarnow l. ,hansen t. ,gaede p. ,jorsal a. ,ng d.p.k. ,ikeda m. ,yanagimoto t. ,tsunoda t. ,unoki h. ,kawai k. ,imanishi m. ,suzuki d. ,shin h.d. ,park k.s. ,kashiwagi a. ,iwamoto y. ,kaku k. ,kawamori r. ,parving h.-h. ,bowden d.w. ,pedersen o. ,nakamura y.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 2
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چکیده
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It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. a large-scale genotyping analysis of gene-based single nucleotide polymorphisms (snps) in japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme a carboxylase beta (acacb) as a candidate for a susceptibility to diabetic nephropathy; the landmark snp was found in the intron 18 of acacb (rs2268388: intron 18 +4139 c > t,p = 1.4x10-6,odds ratio = 1.61,95% confidence interval [ci]: 1.33-1.96). the association of this snp with diabetic nephropathy was examined in 9 independent studies (4 from japan including the original study,one singaporean,one korean,and two european) with type 2 diabetes. one case-control study involving european patients with type 1 diabetes was included. the frequency of the t allele for snp rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. a meta-analysis revealed that rs2268388 was significantly associated with proteinuria in japanese patients with type 2 diabetes (p = 5.35x10-8,odds ratio = 1.61,95% cl: 1.35-1.91). rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (esrd) in european americans (p = 661024,odds ratio = 1.61,95% cl: 1.22-2.13). significant association was not detected between this snp and nephropathy in those with type 1 diabetes. a subsequent in vitro functional analysis revealed that a 29-bp dna fragment,including rs2268388,had significant enhancer activity in cultured human renal proximal tubular epithelial cells. fragments corresponding to the disease susceptibility allele (t) had higher enhancer activity than those of the major allele. these results suggest that acacb is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes. © 2010 maeda et al.
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آدرس
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laboratory for endocrinology and metabolism,riken center for genomic medicine,yokohama,kanagawa, Japan, laboratory for endocrinology and metabolism,riken center for genomic medicine,yokohama,kanagawa,japan,discovery research laboratories,shionogi and co.,toyonaka,osaka, Japan, department of medicine,shiga university of medical science,otsu,shiga, Japan, diabetes center,tokyo women's medical university,tokyo, Japan, wake forest university school of medicine,winston-salem,nc, United States, wake forest university school of medicine,winston-salem,nc, United States, wake forest university school of medicine,winston-salem,nc, United States, division of nephrology and metabolism,department of internal medicine,tokai university school of medicine,isehara,kanagawa, Japan, division of nephrology and metabolism,department of internal medicine,tokai university school of medicine,isehara,kanagawa, Japan, steno diabetes center,hagedorn research institute,gentofte, Denmark, steno diabetes center,hagedorn research institute,gentofte,denmark,faculty of health sciences,university of southern denmark,odense, Denmark, steno diabetes center,hagedorn research institute,gentofte, Denmark, steno diabetes center,hagedorn research institute,gentofte, Denmark, department of epidemiology and public health,national university of singapore, Singapore, developmental research laboratories,shionogi and co.,toyonaka,osaka, Japan, developmental research laboratories,shionogi and co.,toyonaka,osaka, Japan, laboratory for medical informatics,riken center for genomic medicine,yokohama,kanagawa, Japan, laboratory for endocrinology and metabolism,riken center for genomic medicine,yokohama,kanagawa, Japan, kawai clinic,tsukuba,ibaraki, Japan, division of nephrology and hypertension,department of internal medicine,osaka city general hospital,osaka, Japan, division of nephrology and metabolism,department of internal medicine,tokai university school of medicine,isehara,kanagawa, Japan, department of life science,sogang university,seoul, South Korea, department of molecular medicine and biopharmaceutical sciences,graduate school of convergence science and technology,seoul national university,seoul,south korea,department of internal medicine,college of medicine,seoul national university,seoul, South Korea, department of medicine,shiga university of medical science,otsu,shiga, Japan, diabetes center,tokyo women's medical university,tokyo, Japan, division of endocrinology and metabolism,department of internal medicine,kawasaki medical school,kurashiki,okayama, Japan, department of medicine,metabolism and endocrinology,school of medicine,juntendo university,tokyo, Japan, faculty of health sciences,university of aarhus,aarhus,denmark,department of medical endocrinology,rigshospitalet,copenhagen, Denmark, wake forest university school of medicine,winston-salem,nc, United States, steno diabetes center,hagedorn research institute,gentofte,denmark,faculty of health sciences,university of aarhus,aarhus,denmark,institute of biomedical sciences,faculty of health sciences,university of copenhagen,copenhagen, Denmark, laboratory of molecular medicine,institute of medical science,university of tokyo,tokyo, Japan
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Authors
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