التفاصيل البيبلوغرافية
| العنوان: |
Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. |
| المؤلفون: |
Teumer, Alexander, Tin, Adrienne, Sorice, Rossella, Gorski, Mathias, Nan Cher Yeo, Chu, Audrey Y., Man Li, Yong Li, Mijatovic, Vladan, Yi-An Ko, Taliun, Daniel, Luciani, Alessandro, Ming-Huei Chen, Qiong Yang, Foster, Meredith C., Olden, Matthias, Hiraki, Linda T., Tayo, Bamidele O., Fuchsberger, Christian, Dieffenbach, Aida Karina |
| المصدر: |
Diabetes; Mar2016, Vol. 65 Issue 3, p803-817, 15p, 2 Charts, 3 Graphs |
| مصطلحات موضوعية: |
ALBUMINS, KIDNEY diseases, CARDIOVASCULAR diseases, CUBILIN, SINGLE nucleotide polymorphisms, PROTEIN metabolism, TYPE 2 diabetes complications, ALBUMINURIA, ANIMAL experimentation, CELL receptors, DIABETES, DIABETIC nephropathies, DISEASE susceptibility, GENETIC polymorphisms, GENETIC techniques, KIDNEY tubules, KIDNEYS, META-analysis, TYPE 2 diabetes, PROTEINS, PROTEOLYTIC enzymes, RATS, RESEARCH funding, TRANSFERASES, SEQUENCE analysis |
| مستخلص: |
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. [ABSTRACT FROM AUTHOR] |
|
Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder