{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:30:15Z","timestamp":1773657015479,"version":"3.50.1"},"reference-count":31,"publisher":"American Diabetes Association","issue":"4","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:p>A polymorphism in the ecto-nucleotide pyrophosphatase\/phosphodiesterase 1 gene (ENPP1) (previously known as PC-1), resulting in an amino acid change from lysine to glutamine at codon 121 (K121Q), is associated with insulin resistance. A small follow-up study of patients with type 1 diabetes and proteinuria found that renal function declines more rapidly in carriers of the Q variant than in noncarriers. To examine this finding further, we conducted a large case-control study and a family-based study. Genomic DNA was obtained from 659 patients: 307 with normal urinary albumin excretion despite diabetes duration of &amp;gt;15 years (control subjects) and 352 with advanced diabetic nephropathy, of whom 200 had persistent proteinuria and 152 had end-stage renal disease (ESRD). Individuals were genotyped for Q and K variants using a previously described protocol. The frequency of Q variant carriers was 21.5% in control subjects, 31.5% in subjects with proteinuria, and 32.2% in subjects with ESRD (P = 0.012). In a stratified analysis according to duration of diabetes, the risk of early-onset ESRD for carriers of the Q variant was 2.3 times that for noncarriers (95% CI, 1.2\u20134.6). The Q variant was not associated with late-onset ESRD. Similar findings were obtained in a family-based study. We conclude that carriers of the Q variant of ENPP1 are at increased risk for developing ESRD early in the course of type 1 diabetes.<\/jats:p>","DOI":"10.2337\/diabetes.51.4.1188","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1188-1193","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":43,"title":["Polymorphism in Ecto-Nucleotide Pyrophosphatase\/Phosphodiesterase 1 Gene (<i>ENPP1\/PC-1<\/i>) and Early Development of Advanced Diabetic Nephropathy in Type 1 Diabetes"],"prefix":"10.2337","volume":"51","author":[{"given":"Luis H.","family":"Canani","sequence":"first","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.K.","family":"Ng","sequence":"additional","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Smiles","sequence":"additional","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Rogus","sequence":"additional","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Warram","sequence":"additional","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej S.","family":"Krolewski","sequence":"additional","affiliation":[{"name":"From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031223011249900_R1","doi-asserted-by":"crossref","unstructured":"Krolewski AS: Genetics of diabetic nephropathy: evidence for major and minor gene effects. 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