{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:33:23Z","timestamp":1768736003401,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2004,6,25]],"date-time":"2004-06-25T00:00:00Z","timestamp":1088121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetic Medicine"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aims\u2003<\/jats:bold> Protein kinase C (PKC), a serine\/threonine kinase, is known to be activated in various tissues under hyperglycaemic conditions. Notably, PKC\u03b2, a member of the conventional PKC group, is the predominant isoform detected in vascular tissues and could be involved in the development of diabetic vascular complications. In the present study, we investigated genetic variations in the 5\u2032\u2010upstream region of the PKC\u03b2 gene to assess their possible relation to vascular complications in diabetic patients.<\/jats:p><jats:p><jats:bold>Methods\u2003<\/jats:bold> Variations upstream from the PKC\u03b2 gene (\u22121066\/+256) were examined in 60 Type 2 diabetic patients using a cycle sequencing method. Screening of detected variations was performed in 204 Type 2 diabetic patients and 160 healthy controls.<\/jats:p><jats:p><jats:bold>Results\u2003<\/jats:bold> Five single nucleotide polymorphisms; C(\u2212238)G, C(\u2212287)T, A(\u2212348)G, C(\u2212546)G, and C(\u2212853)T, were identified in the upstream region. The C(\u2212287)T and A(\u2212348)G polymorphisms were in perfect linkage disequilibrium. There were no significant differences in genotype or allele frequencies of the five polymorphisms among the diabetic patients and healthy subjects. However, both \u2212238GG and \u2212287CC (\u2212348GG) homozygotes showed significantly higher frequencies of macrovascular disease compared with patients with other genotypes. Further, an electrophoretic mobility shift assay revealed that the \u2212238G fragment had a five\u2010fold higher affinity for transcription factor Sp1 when compared with \u2212238C.<\/jats:p><jats:p><jats:bold>Conclusions\u2003<\/jats:bold> The C(\u2212238)G and C(\u2212287)T\u2010A(\u2212348)G polymorphisms in the 5\u2032\u2010upstream region of the PKC\u03b2 gene may have an effect on the susceptibility of diabetic vascular complications through an alteration of tissue PKC\u03b2 density or function.<\/jats:p>","DOI":"10.1111\/j.1464-5491.2004.01304.x","type":"journal-article","created":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T15:37:16Z","timestamp":1095867436000},"page":"1113-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Polymorphisms in the 5\u2032\u2010upstream region of the PKC\u03b2 gene in Japanese patients with Type 2 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