{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:20:13Z","timestamp":1791080413337,"version":"4.1.0"},"reference-count":69,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:p>BACKGROUND\u2014 Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014 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.<\/jats:p>\n               <jats:p>RESULTS\u2014 We observed association between rs17880135 in the 3\u2032 region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64\u20134.18], P = 5.6 \u00d7 10\u22125, q = 0.06) and persistent microalbuminuria (1.82 [1.29\u20132.57], P = 6.4 \u00d7 10\u22124, q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P &amp;lt; 10\u22123) 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.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014 Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT\/EDIC study.<\/jats:p>","DOI":"10.2337\/db07-1059","type":"journal-article","created":{"date-parts":[[2007,10,4]],"date-time":"2007-10-04T01:10:06Z","timestamp":1191460206000},"page":"218-228","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":74,"title":["Multiple Superoxide Dismutase 1\/Splicing Factor Serine Alanine 15 Variants Are Associated With the Development and Progression of Diabetic Nephropathy"],"prefix":"10.2337","volume":"57","author":[{"given":"Hussam","family":"Al-Kateb","sequence":"first","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Boright","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Mirea","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Prosserman Centre for Health Research, Toronto, Ontario, Canada"},{"name":"Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Xie","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Prosserman Centre for Health Research, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinku","family":"Sutradhar","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Prosserman Centre for Health Research, Toronto, Ontario, Canada"},{"name":"Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Mowjoodi","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupinder","family":"Bharaj","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Liu","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M.","family":"Bucksa","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie L.","family":"Arends","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Steffes","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Cleary","sequence":"additional","affiliation":[{"name":"The Biostatistics Center, The George Washington University, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjie","family":"Sun","sequence":"additional","affiliation":[{"name":"The Biostatistics Center, The George Washington University, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Lachin","sequence":"additional","affiliation":[{"name":"The Biostatistics Center, The George Washington University, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Thorner","sequence":"additional","affiliation":[{"name":"Division of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Jayne","family":"McKnight","sequence":"additional","affiliation":[{"name":"Nephrology Research Group, Queen's University of Belfast, Belfast, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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