التفاصيل البيبلوغرافية
| العنوان: |
Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated With the Development and Progression of Diabetic Nephropathy. |
| المؤلفون: |
Al-Kateb, Hussam, Boright, Andrew P., Mirea, Lucia, Xie, Xinlei, Sutradhar, Rinku, Mowjoodi, Alireza, Bharaj, Bhupinder, Liu, Michelle, Bucksa, Jean M., Arends, Valerie L., Steffes, Michael W., Cleary, Patricia A., Sun, Wanjie, Lachin, John M., Thorner, Paul S., Ho, Michael, McKnight, Amy Jayne, Maxwell, A. Peter, Savage, David A., Kidd, Kenneth K. |
| المصدر: |
Diabetes; Jan2008, Vol. 57 Issue 1, p218-228, 11p, 1 Color Photograph, 5 Charts, 2 Graphs |
| مصطلحات موضوعية: |
GENES, DIABETIC nephropathies, SUPEROXIDE dismutase, SERINE, ALANINE |
| مستخلص: |
BACKGROUND--Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS--We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS--We observed association between rs17880135 in the 3′ region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64-4.18], P = 5.6 x 10-5, q = 0.06) and persistent microalbuminuria (1.82 [1.29-2.57], P = 6.4 x 10-4, q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10-3) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS--Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study. Diabetes 57:218-228, 2008 [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