| pubmed-article:18458324 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C0015392 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C0022646 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C0009566 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C0205082 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C1366564 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C0086860 | lld:lifeskim |
| pubmed-article:18458324 | lifeskim:mentions | umls-concept:C1882417 | lld:lifeskim |
| pubmed-article:18458324 | pubmed:issue | 19 | lld:pubmed |
| pubmed-article:18458324 | pubmed:dateCreated | 2008-5-14 | lld:pubmed |
| pubmed-article:18458324 | pubmed:abstractText | Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 x 10(-3); Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 x 10(-8); and Boston: P = 2.1 x 10(-2)]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications. | lld:pubmed |
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| pubmed-article:18458324 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18458324 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18458324 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18458324 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18458324 | pubmed:month | May | lld:pubmed |
| pubmed-article:18458324 | pubmed:issn | 1091-6490 | lld:pubmed |
| pubmed-article:18458324 | pubmed:author | pubmed-author:LevyJ BJB | lld:pubmed |
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| pubmed-article:18458324 | pubmed:author | pubmed-author:YangZhenglinZ | lld:pubmed |
| pubmed-article:18458324 | pubmed:author | pubmed-author:ZhangKangK | lld:pubmed |
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| pubmed-article:18458324 | pubmed:author | pubmed-author:ChenYuhongY | lld:pubmed |
| pubmed-article:18458324 | pubmed:author | pubmed-author:XianYangY | lld:pubmed |
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| pubmed-article:18458324 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18458324 | pubmed:day | 13 | lld:pubmed |
| pubmed-article:18458324 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:18458324 | pubmed:owner | NLM | lld:pubmed |
