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A POLYMORPHISM IN THE UPSTREAM REGION OF THE PKC
BETA GENE IS ASSOCIATED WITH MACROVASCULAR
DISEASES IN JAPANESE PATIENTS WITH TYPE 2 DIABETES
Y. Ikeda, T. Suehiro, F. Osaki, S. Tsuzura, Y. Kumon, K. Hashimoto
Kochi Medical School, Nankoku, Kochi, Japan
Protein kinase C (PKC), a serine/threonine kinase, is involved in signal
transduction, tumor promotion, gene expression, and cell proliferation and
differentiation. PKC beta is the predominant isoform detected in vascular
smooth muscle cells, and is supposed to regulate the cell cycle. Therefore,
genetic alterations of PKC beta may be involved in the susceptibility of
diabetic vascular complications. To elucidate this issue, we investigated
polymorphisms in the 5’-flanking region of the PKC beta gene in 195 patients
with type 2 diabetes and 111 normal subjects, and examined its association
with diabetic macroangiopathies. A MspI polymorphism was detected in the
upstream fragment (820 bp) by a direct sequencing method. There was no
difference in the allelic frequency between the patients (0.70 and 0.30 for the
A and G allele, respectively) and normal subjects (0.73 and 0.27,
respectively). Among the patients, however, frequency of macrovascular
diseases including coronary heart disease, cerebrovascular disease, and
peripheral artery disease, was significantly lower in patients with A allele
than in those without (16.9% and 44.4%, respectively, p=0.005). This
polymorphism localized in the 5’-flanking region of the PKC beta gene,
likely in the promoter region of the gene, and may therefore be involved in
the regulation of tissue PKC beta density. The genetic variation of PKC beta
may be associated with a difference in the susceptibility of vascular
complications in diabetic patients.