- Association of the Polymorphisms in the PSMA6 (rs1048990) and PSMB5 (rs2230087) Genes with Type 2 Diabetes in Korean Subjects.
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Hee Kyoung Kim, Su Won Kim, Yun Jeong Doh, Sae Rom Kim, Mi Kyung Kim, Keun Gyu Park, Hye Soon Kim, Kyong Soo Park, Min Yoo, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
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Korean Diabetes J. 2008;32(3):204-214. Published online June 1, 2008
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DOI: https://doi.org/10.4093/kdj.2008.32.3.204
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- BACKGROUND
The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.
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Citations
Citations to this article as recorded by  - Ubiquitin-proteasome system in diabetic retinopathy
Zane Svikle, Beate Peterfelde, Nikolajs Sjakste, Kristine Baumane, Rasa Verkauskiene, Chi-Juei Jeng, Jelizaveta Sokolovska
PeerJ.2022; 10: e13715. CrossRef - 1,4‐Dihydropyridine derivatives without Ca2+‐antagonist activity up‐regulate Psma6 mRNA expression in kidneys of intact and diabetic rats
Kristīne Ošiņa, Evita Rostoka, Jelizaveta Sokolovska, Natalia Paramonova, Egils Bisenieks, Gunars Duburs, Nikolajs Sjakste, Tatjana Sjakste
Cell Biochemistry and Function.2016; 34(1): 3. CrossRef - Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals
Tatjana Sjakste, Natalia Paramonova, Kristine Osina, Kristine Dokane, Jelizaveta Sokolovska, Nikolajs Sjakste
Molecular Genetics and Genomics.2016; 291(2): 891. CrossRef
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