한국인에서 PSMA6 (rs1048990)와 PSMB5 (rs2230087) 유전자 다형성과 제2형 당뇨병과의 연관성

• Published in: Diabetes & metabolism journal Vol. 32; no. 3; pp. 204 - 214
• Main Authors: 김희경, Hee Kyoung Kim, 김수원, Su Won Kim, 도윤정, Yun Jeong Doh, 김새롬, Sae Rom Kim, 김미경, Mi Kyung Kim, 박근규, Keun Gyu Park, 김혜순, Hye Soon Kim, 박경수, Kyong Soo Park, 유민, Min Yoo, 김정국, Jung Guk Kim, 김보완, Bo Wan Kim, 이인규, I
• Format: Journal Article
• Language: Korean
• Published: 대한당뇨병학회 30.06.2008
• Subjects: Polymorphism; Proteasome subunit a type 6; Proteasome subunit β type 5 gene; Type 2 diabetes; Ubiquitin-proteasome system
• ISSN: 2233-6079; 2233-6087

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 a type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of I kB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of I kB 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 B 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.