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摘要:
Over 50 single nucleotide polymorphisms (SNPs) have been identified by genome wide association studies (GWAS) to be associated with susceptibility to type 2 diabetes (T2D);however the causal gene in most cases is not known. In this study we sought to identify which may be the most likely causal genes at five T2D GWAS loci by measuring their expression in control and T2D islets, as well as observing their regulation by glucose. We measured the expression of ten genes at five loci (CDKN2A/2B, CDC123/CAMK-1D, HHEX/IDE, TSPAN8/LGR5, and DGKB/TMEM 195), in control and human pancreatic islets by real-time PCR. We then measured the expression of these genes in the rodent pancreatic beta cell line INS-1 exposed to 5.6 mmol/l, 11 mmol/l and 28 mmol/l glucose for 48 hours. We found differential expression of the longest isoform of CDKN2B specifically between control and T2D human islets, whereas the shortest isoform of this gene had no expression in islets. Tmem195 was the only gene to show differential expression in response to increasing glycemia in INS-1 cells under the conditions described. Our study is an example of how the differential expression of genes in loci spanning more than one gene can aid identification of the more likely causal gene.
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篇名 Expression profiling of putative type 2 diabetes susceptibility genes in human islets and in rat beta cell lines
来源期刊 糖尿病(英文) 学科 医学
关键词 Human Type 2 DIABETES ISLET GWAS GENE Expression
年,卷(期) 2013,(1) 所属期刊栏目
研究方向 页码范围 27-32
页数 6页 分类号 R73
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Human
Type
2
DIABETES
ISLET
GWAS
GENE
Expression
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期刊影响力
糖尿病(英文)
季刊
2160-5831
武汉市江夏区汤逊湖北路38号光谷总部空间
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293
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